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Public Disclosure Synopsis Protocol A3841064 – 30 May 2014 – Final

PFIZER INC.

These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved package insert.

PROPRIETARY DRUG NAME® / GENERIC DRUG NAME: Caduet ® / Amlodipine besylate/Atorvastatin calcium

PROTOCOL NO.: A3841064

PROTOCOL TITLE: A Multi-Center, Open Label Study to Evaluate Long Term Safety of Caduet in Patient With Both of Hypertension and Hypercholesterolemia, or With Both of Angina Pectoris and Hypercholesterolemia

Study Centers: A total of twenty (20) centers in Japan took part in the study and enrolled subjects.

Study Initiation Date and Final Completion Date: 30 August 2010 to 18 February 2012 Phase of Development: Phase 4

Study Objectives:

Primary Objective: The primary objective was to investigate the safety of amlodipine/atorvastatin 2.5 mg/5 mg, 2.5 mg/10 mg, 5 mg/5 mg or 5 mg/10 mg during 52 week treatment period.

Secondary Objectives: The secondary objective was to investigate percent changes in low density lipoprotein cholesterol (LDL-C) and changes in trough systolic blood pressure (SBP) from baseline at each visit as the efficacy of amlodipine/atorvastatin combination tablets. In addition, percent changes in total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), and changes in apolipoprotein B, LDL-C/HDL-C and TC/HDL-C ratios and trough diastolic blood pressure (DBP) from baseline at each visit were investigated.

METHODS

Study Design: This was a multicenter, open-label study to evaluate the long-term safety profile of amlodipine/atorvastatin (2.5 mg/5 mg, 2.5 mg/10 mg, 5 mg/5 mg or 5 mg/10 mg doses).

The trial consisted of 2 parts: a screening period and a treatment period. Subjects who met the eligibility criteria were enrolled in the treatment period, where subjects receiving a combination therapy of amlodipine and atorvastatin or amlodipine monotherapy were switched to one of the amlodipine/atorvastatin tablets (2.5 mg/5 mg, 2.5 mg/10 mg, 5 mg/5 mg and 5 mg/10 mg). For each subject, the dose of amlodipine contained in amlodipine/atorvastatin at Visit 1 was same as that used during the screening period. For

Template version 1.1


subjects who took atorvastatin during the screening period and whose LDL-C level at Visit 0 was <160 mg/dL, the dose of atorvastatin contained in amlodipine/atorvastatin at Visit 1 was same as that used during the screening period. For subjects who took atorvastatin 5 mg during the screening period and whose LDL-C level at Visit 0 was ≥160 mg/dL, the dose of atorvastatin contained in amlodipine/atorvastatin at Visit 1 was increased to 10 mg. For subjects who were untreated for hypercholesterolemia during the screening period (ie, subjects who had not received any statin therapy for at least 3 months during the previous year), the dose of atorvastatin contained in amlodipine/atorvastatin was determined by the Investigator. Figure 1 shows the study plan.



Figure 1 Study Design

Caduet = amlodipine/atorvastatin. BP = Blood pressure; DBP = Diastolic blood pressure; LDL-C = Low density lipoprotein cholesterol; SBP = Systolic blood pressure; V = Visit; W = week. 1) Use of other antihypertensives than amlodipine was allowed on the condition that the same dose was

used for at least 4 weeks before the start of the study treatment and the dosage regimen should not be modified during the study.

2) SBP and DBP levels at V1 (Week 0). 3) LDL-C level at V0 (Week −2).

In the case of the subjects not achieving the target LDL-C level or BP levels after Week 12 (Visit 5), a change in the dose of amlodipine/atorvastatin may have been allowed at the Investigator's discretion at Week 12 (Visit 5).

The schedule of study activities is summarized in Table 1.



Table 1. Schedule of Activities

Screening Period Treatment Period

Week -2 0 2 4 8 12 16 20 24 28 32 36 40 44 48 52 (Allowance) ±7 d ±3d ±3d ±7d ±7d ±7d ±7d ±7d ±7d ±7d ±7d ±7d ±7d ±7d ±7 d

Visit Point V0 V1 V2 V3 V4 V5 V6 V7 V8 V9 V10 V11 V12 V13 V14 V15 (Discontinued)a

Informed consent X Confirmation of in/ex criteria X X Medical history X Vital signs (BPb and HR) X X X X X X X X X X X X X X X X Height, body weight X Pregnancy test (urine) c X X Physical examinations X Evaluation of adverse events (AE) X X X X X X X X X X X X X X Serious adverse events (SAE) X X X X X X X X X X X X X X X X Hematologyd X X X X X Biochemical examinatione X X X X X X Urinalysis (general test) f X X X X X 12-lead ECG ← X → X Checking AP conditiong X X X X X X X X X X X X X X X X Lipid parametersh X X X X X X PWV and/or CAVIi X X X Hs-CRP X X X Exploratory bio-markersj X X X Pharmacogenomic sampling (PGx)k ← X →

Prescription of the study drug X X X X X X X X X X X X X X Concomitant drugs and therapy X X X X X X X X X X X X X X X X Compliance checking X X X X X X X X X X X X X X ← X →: Measurements were to be performed during the period. AP = angina pectoris; BP = blood pressure; CAVI = cardio ankle vascular index; d = days; ECG = electrocardiogram; HR = heart rate; Hs-CRP = high-sensitivity C-reactive protein; PGx = pharmacogenomic; PWV = pulse wave velocity; V = visit.



Table 1. Schedule of Activities

a. If a subject permanently discontinued study prior to Week 52, the procedure scheduled to be performed at Week 52 visit was to be completed if possible.

b. Trough blood pressure (BP) in the sitting position was measured after the subject remained sitting for 5 minutes, at Visit 1 (Week 0) to Visit 15 (Week 52). At Visit 0 (Week -2), the Investigator instructed the subject that administration of both amlodipine and atorvastatin on the day of the study visit as above, was pending until the instruction by the Investigator had been made, due to the trough BP being measured.

c. This was mandatory for women of childbearing potential (WOCBP). d. White blood cell count, lymphocyte subsets (lymphocytes, monocytes, basophils, eosinophils, neutrophils), red blood cell count, hemoglobin,

hematocrit, platelet count. e. Total protein (TP), total bilirubin (T-Bil), albumin (Alb), blood urea nitrogen (BUN), serum creatinine (sCr), aspartate aminotransferase (AST),

alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), sodium (Na+), potassium (K+), chloride (Cl－), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), urine analysis (UA).

f. Protein, glucose, occult blood. g. Checking clinical condition of angina pectoris (eg, angina episodes happen more often, numbers of nitrate usage, or last longer than usual etc. were

measured and recorded). h. Total cholestrol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and apolipoprotein B. i. Pulse Wave Velocity (PWV) was conducted as a prioritized measurement. If feasible both PWV and cardio ankle vascular index (CAVI) were

performed. j. Malondialdehyde-modified low density lipoprotein (MDA-LDL) and 8-hydroxydeoxyguanosine (8-OHdG). k. Pharmacogenomics were conducted if possible (separate molecular profiling consent had to be obtained for pharmacogenomic sampling).



Number of Subjects (Planned and Analyzed): It was planned to enroll approximately 150 subjects in the study. A total of 159 subjects (143 subjects with both hypertension and hypercholesterolemia and 16 subjects with both angina pectoris and hypercholesterolemia) were enrolled and treated. Diagnosis and Main Criteria for Inclusion: Male and female subjects aged 20 years and older with both hypertension and hypercholesterolemia, or both angina pectoris and hypercholesterolemia, who took amlodipine 2.5 mg/day or 5 mg/day for at least 28 days before Week -2 with a well-controlled BP value (BP value <140/90 mmHg at Week 0), and clinically stable angina pectoris (subjects with hypercholesterolemia and angina pectoris only). In addition, subjects had to meet one of the following criteria: 1) took atorvastatin 5 mg/day or 10 mg/day for at least 28 days before Week -2; or 2) were statin-naïve, defined as receiving no statin therapy for at least 3 months during the previous 12 months, with LDL-C level ≥160 mg/dL and <250 mg/dL, and TG level <400 mg/dL at Week -2.

Subjects who needed 3 or more multi-antihypertensive therapies to achieve the target BP level (defined as SBP <140 mmHg and DBP <90 mmHg) or with uncontrolled status of hypertension at Week 0 (Visit 1), and subjects who had uncontrolled or uncontrollable status of hypercholesterolemia at Week -2 (LDL-C ≥ 160 mg/dL) even though atorvastatin 10 mg was administered, were excluded from the study.

Study Treatment: One amlodipine/atorvastatin tablet of the specified strength (2.5 mg/5 mg, 2.5 mg/10 mg, 5 mg/5 mg, or 5 mg/10 mg) was administered once daily after breakfast, in principle, for 52 weeks. Each subject was asked to visit the study site at the same time as far as possible, in the morning (in principle), at every visit. Subjects made each visit without taking breakfast to maintain the fasting state for at least 10 hours after the evening meal on the preceding day. Subjects took the investigational product on the preceding day of each visit scheduled for blood pressure monitoring, but did not take the morning dose on the day of a visit.

Efficacy and Safety Endpoints:

Primary Endpoints: The primary efficacy endpoint in this study was safety.

Secondary Endpoints: Secondary efficacy endpoints are shown below:

Changes in the following parameters from baseline (Visit 1, Week 0) were investigated at each assessment point [Visit 2 (Week 2), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44), Visit 14 (Week 48), and Visit 15 (Week 52)]:

• Changes in trough SBP

• Changes in trough DBP



Changes in the following parameters from baseline (Visit 1, Week 0) were investigated at each assessment point [Visit 3 (Week 4), Visit 5 (Week 12), Visit 8 (Week 24), and Visit 15 (Week 52)]:

• Percent changes and changes in LDL-C

• Percent changes and changes in TC, HDL-C, and TG

• Changes in LDL-C/HDL-C and TC/HDL-C ratios

• Percent changes and changes in apolipoprotein B

Safety Evaluations:

Adverse events (AEs) were monitored between the first day of study treatment and the last day of a visit, and were recorded in the case report form. Serious adverse events (SAEs) were reported between the day of informed consent and 28 days after the last dose of study treatment. The laboratory tests, excluding serum lipids for efficacy endpoints, were performed at Visit 0 (Week -2), Visit 1 (Week 0), Visit 5 (Week 12), Visit 8 (Week 24), and Visit 15 (Week 52 or at withdrawal). In addition, at Visit 3 (Week 4), only a blood chemistry test was performed. Conditions of angina pectoris at Visit 1 (Week 0) and at each observation were compared, and it was determined whether there was clinically significant worsening. Twelve-lead electrocardiograms were measured at Visit 0 (Week -2) or Visit 1 (Week 0), and Visit 15 (Week 52 or at withdrawal), and pulse rates were measured at all visits between Visit 0 (Week -2) and Visit 15 (Week 52 or at withdrawal).

Statistical Methods: The efficacy analysis set included all subjects who received at least 1 dose of study drug and contributed data to baseline and at least 1 post-baseline efficacy assessment. The safety analysis set included all subjects who received at least 1 dose of study drug.

Blood pressure was analyzed by subgroup (subjects with both hypertension and hypercholesterolemia, and subjects with both angina pectoris and hypercholesterolemia). Actual values and changes from baseline in SBP and DBP at each time point were summarized using descriptive statistics and 2-sided 95% confidence interval of the mean.

With regard to lipids, actual values, percent changes and changes from baseline in LDL-C, TC, TG, HDL-C and apolipoprotein B at each time point were summarized using descriptive statistics and 2-sided 95% CI of the mean. Actual values and changes from baseline in the ratio of LDL-C to HDL-C and the ratio of TC to HDL-C at each time point were also summarized by summary statistics and 2-sided 95% CI of the mean.

All the analyses on safety were performed in the safety analysis set. Safety endpoints were established in compliance with the Sponsor's Data Standards. AEs were coded into system organ classes and preferred terms using Medical Dictionary for Regulatory Activities version 14.1.



Subject Disposition and Demography: In this study, 159 subjects were enrolled, and all the subjects received the study drug. Fourteen (14) subjects (8.8%) discontinued the study, namely due to withdrawal of consent (4 subjects, 2.5%), non treatment-related AEs (5 subjects, 3.1%), treatment-related AEs (3 subjects, 1.9%), and other reasons (2 subjects, 1.3%, 1 subject was arrested and the other subject had difficulty visiting the study site due to treatment of complications). Of 159 subjects, 143 subjects were subjects with both hypertension and hypercholesterolemia and 16 subjects were subjects with both angina pectoris and hypercholesterolemia (including those with all of angina pectoris, hypertension and hypercholesterolemia). In this study, these 16 subjects all had angina pectoris, hypertension and hypercholesterolemia. Of all the subjects, 145 subjects (91.2%) completed the study, consisting of 130 subjects (90.9%) with both hypertension and hypercholesterolemia and 15 subjects (93.8%) with angina pectoris, hypertension and hypercholesterolemia (Table 2).

Table 2. Disposition of Subjects and Analysis Populations

Number of Subjects (%) All Subjects Subjects With Both Hypertension and

Hypercholesterolemia

Subjects With all of Angina Pectoris,

Hypertension and Hypercholesterolemia

Assigned to study treatment 159 143 16 Treated 159 (100) 143 (100) 16 (100) Completed 145 (91.2) 130 (90.9) 15 (93.8) Discontinued 14 (8.8) 13 (9.1) 1 (6.3)

Withdrawal of consent 4 (2.5) 4 (2.8) 0 Non treatment-related AEs 5 (3.1) 4 (2.8) 1 (6.3) Treatment-related AEs 3 (1.9) 3 (2.1) 0 Others 2 (1.3)a 2 (1.4) a 0

Analyzed for efficacy 158 (99.4) 142 (99.3) 16 (100) Analyzed for safety

AEs 159 (100) 143 (100) 16 (100) Laboratory test 159 (100) 143 (100) 16 (100)

AE = adverse event. a. One subject was arrested and the other subject had difficulty visiting the study site due to treatment of

complications.

Demographic characteristics are provided in summarized in Table 3. Of 159 subjects, 108 subjects (67.9%) were female. The average age of the subjects was 65.0 years. Subjects aged 65 years or older accounted for 56.0% of all the subjects. The average body weight was 61.2 kg and the average body mass index was 24.9 kg/m2.



Table 3. Demographic Characteristics

Characteristics Amlodipine/Atorvastatin Male Female Total

Number (%) of Subjects 51 108 159 Age (years)

<18 0 0 0 18-44 4 (7.8) 1 (0.9) 5 (3.1) 45-64 21 (41.2) 44 (40.7) 65 (40.9) ≥65 26 (51.0) 63 (58.3) 89 (56.0) Mean 63.5 65.7 65.0 SD 11.9 8.0 9.5 Range 31-87 41-84 31-87

Race Asian 51 (100.0) 108 (100.0) 159 (100.0)

Weight (kg) Mean 69.7 57.1 61.2 SD 9.6 10.0 11.5 Range 51.0-89.9 36.8-92.1 36.8-92.1 N 51 (100.0) 108 (100.0) 159 (100.0)

Body mass index (kg/m2) Mean 25.2 24.7 24.9 SD 3.0 3.9 3.6 Range 19.4-33.1 16.2-38.9 16.2-38.9 N 51 (100.0) 108 (100.0) 159 (100.0)

Height (cm) Mean 166.4 151.9 156.6 SD 5.8 5.3 8.7 Range 152.0-180.2 133.0-163.1 133.0-180.2 N 51 (100.0) 108 (100.0) 159 (100.0)

Body Mass Index is defined as wt/(ht*.01)**2. N = total number of subjects; SD = standard deviation.

Efficacy Results:

There were no primary efficacy endpoints in this study.

Secondary Efficacy Endpoints:

The mean values of SBP and DBP generally changed to below baseline and were well-controlled throughout the study period, regardless of the presence/absence of angina pectoris. A summary of actual value and change from baseline in SBP endpoints at each visit is shown in Table 4. A summary of actual value and change from baseline in DBP endpoints at each visit is shown in Table 5.



Table 4. Summary of Actual Value and Change From Baseline in Blood Pressure Endpoints at Each Visit (by Primary Diagnoses) - Systolic Blood Pressure (mmHg)

Assessment Time Point Statistics

Amlodipine/Atorvastatin Subject Population by Primary Diagnoses

Hypertension/ Hypercholesterolemiaa

Angina Pectoris/ Hypercholesterolemiab

Actual Value Change From Baseline


Baselinec - N 142 - 16 - Mean 127.2 - 129.9 - Std. Dev 9.25 - 8.39 - 95% CI (125.7, 128.7) - (125.4, 134.4) - Median 128.5 - 133.8 - Min 102.0 - 109.5 - Max 139.0 - 138.5 -

Week 2 (Day 14) N 140 140 15 15 Mean 127.0 -0.2 128.5 -1.1 Std. Dev 10.40 8.57 14.38 11.57 95% CI (125.3, 128.8) (-1.6, 1.2) (120.6, 136.5) (-7.5, 5.3) Median 128.3 0.0 135.5 1.0 Min 95.0 -22.0 99.0 -37.5 Max 148.0 21.0 143.5 12.0

Week 4 (Day 28) N 139 139 16 16 Mean 126.6 -0.6 127.6 -2.3 Std. Dev 11.32 9.19 12.00 8.68 95% CI (124.7, 128.5) (-2.1, 1.0) (121.2, 134.0) (-7.0, 2.3) Median 127.0 -1.0 126.5 -3.5 Min 96.5 -22.0 106.0 -16.5 Max 157.0 26.0 146.0 13.0

Week 8 (Day 56) N 140 140 16 16 Mean 127.2 0.0 128.8 -1.1 Std. Dev 11.84 10.38 11.20 7.76 95% CI (125.3, 129.2) (-1.8, 1.7) (122.9, 134.8) (-5.2, 3.1) Median 126.3 -1.0 128.8 -0.8 Min 91.0 -31.0 107.0 -13.0 Max 174.5 40.5 147.0 9.0












Week 20 (Day 140) N 136 136 16 16 Mean 124.2 -2.8 127.6 -2.3 Std. Dev 11.10 10.07 12.11 8.47 95% CI (122.3, 126.1) (-4.5, -1.1) (121.2, 134.1) (-6.8, 2.2) Median 123.8 -1.5 129.3 -2.0 Min 97.5 -31.0 105.0 -19.0 Max 152.5 26.0 151.5 15.5

Week 24 (Day 168) N 134 134 16 16 Mean 125.2 -1.8 123.2 -6.7 Std. Dev 10.17 9.74 12.89 9.07 95% CI (123.5, 127.0) (-3.5, -0.2) (116.3, 130.1) (-11.5, -1.9) Median 124.8 -2.3 124.3 -7.5 Min 98.0 -25.5 103.0 -26.5 Max 150.0 24.5 148.5 12.5


Week 32 (Day 224) N 132 132 16 16 Mean 122.0 -4.8 122.1 -7.8 Std. Dev 11.39 10.76 11.69 10.79 95% CI (120.1, 124.0) (-6.7, -3.0) (115.8, 128.3) (-13.6, -2.1) Median 121.3 -5.3 123.0 -5.3 Min 93.5 -36 98.5 -26.5 Max 150.5 30.0 138.5 17.5













Week 48 (Day 336) N 130 130 15 15 Mean 124.6 -2.3 130.1 -0.4 Std. Dev 10.45 10.20 10.63 9.44 95% CI (122.8, 126.4) (-4.1, -0.6) (124.2, 136.0) (-5.6, 4.8) Median 124.0 -2.0 132.0 0.0 Min 102.0 -25.5 104.0 -23.5 Max 148.5 29.5 144.0 20.0











Week 52 (LOCF) N 142 142 16 16 Mean 125.7 -1.5 126.8 -3.1 Std. Dev 10.93 10.81 15.95 13.77 95% CI (123.9, 127.5) (-3.3, 0.3) (118.3, 135.3) (-10.4, 4.3) Median 126.0 -1.0 125.5 -5.0 Min 92.5 -26.5 98.0 -22.0 Max 155.0 23.5 151.0 24.0

CI = confidence interval; LOCF = last observation carried forward; Min = minimum; Max = maximum; N = number of subjects; Std. Dev. = standard deviation. a. Subject population that is defined as the subjects with both hypertension and hypercholesterolemia. b. Subject population that is defined as the subjects with both angina pectoris and hypercholesterolemia

including the subjects with all of angina pectoris, hypertension and hypercholesterolemia. c. Baseline value for each subject is defined as the value of Week 0.



Table 5. Summary of Actual Value and Change From Baseline in Blood Pressure

Endpoints at Each Visit (by Primary Diagnoses) - Diastolic Blood Pressure (mmHg)







Baselinec N 142 - 16 - Mean 78.1 - 78.4 - Std. Dev 6.98 - 7.11 - 95% CI (77.0, 79.3) - (74.6, 82.2) - Median 79.0 - 81.0 - Min 61.5 - 67.0 - Max 88.5 - 88.5 - Week 2 (Day 14) N 140 140 15 15 Mean 78.5 0.3 78.7 0.8 Std. Dev 7.97 7.03 8.10 8.21 95% CI (77.2, 79.8) (-0.8, 1.5) (74.2, 83.2) (-3.8, 5.3) Median 79.3 0.0 79.5 2.5 Min 58.5 -26.0 64.5 -22.5 Max 97.5 23.5 89.0 10.0 Week 4 (Day 28) N 139 139 16 16 Mean 77.8 -0.4 77.3 -1.1 Std. Dev 7.78 6.75 7.19 4.96 95% CI (76.5, 79.1) (-1.5, 0.8) (73.5, 81.1) (-3.8, 1.5) Median 78.5 -0.5 78.8 -1.3 Min 54.0 -18.0 65.5 -8.5 Max 98.0 18.0 89.5 7.5 Week 8 (Day 56) N 140 140 16 16 Mean 78.4 0.2 77.4 -1.0 Std. Dev 8.07 6.90 6.97 6.19 95% CI (77.0, 79.7) (-1.0, 1.3) (73.7, 81.1) (-4.3, 2.3) Median 78.0 0.3 76.0 -1.3 Min 49.5 -24.0 65.5 -11.5 Max 98.5 18.5 91.0 10.5 Week 12 (Day 84) N 140 140 16 16 Mean 78.1 -0.2 77.3 -1.1 Std. Dev 7.70 7.13 6.89 6.86 95% CI (76.8, 79.4) (-1.4, 1.0) (73.6, 81.0) (-4.7, 2.6) Median 79.5 0.0 76.5 1.3 Min 57.0 -20.0 61.5 -13.0 Max 98.0 18.0 86.5 7.5



Table 5. Summary of Actual Value and Change From Baseline in Blood Pressure Endpoints at Each Visit (by Primary Diagnoses) - Diastolic Blood Pressure (mmHg)







Week 16 (Day 112) N 138 138 16 16 Mean 77.5 -0.7 76.2 -2.2 Std. Dev 8.11 7.50 7.33 7.12 95% CI (76.1, 78.9) (-1.9, 0.6) (72.3, 80.1) (-6.0, 1.6) Median 78.3 -0.3 75.8 -3.0 Min 57.5 -20.5 65.5 -12.5 Max 97.0 18.0 89.5 11.5 Week 20 (Day 140) N 136 136 16 16 Mean 76.4 -1.8 77.5 -0.9 Std. Dev 7.54 7.38 6.41 6.71 95% CI (75.1, 77.6) (-3.0, -0.5) (74.1, 80.9) (-4.5, 2.6) Median 76.5 -1.0 78.5 -2.0 Min 52.5 -24.5 66.0 -10.0 Max 91.5 17.0 89.0 8.5 Week 24 (Day 168) N 134 134 16 16 Mean 76.6 -1.6 74.9 -3.5 Std. Dev 7.37 7.03 7.65 6.69 95% CI (75.4, 77.9) (-2.8, -0.4) (70.8, 79.0) (-7.1, 0.1) Median 78.0 -1.0 74.3 -1.0 Min 54.5 -21.0 59.5 -22.0 Max 92.0 14.0 87.5 4.0 Week 28 (Day 196) N 132 132 16 16 Mean 75.6 -2.6 75.4 -3.0 Std. Dev 7.91 7.27 7.15 6.55 95% CI (74.2, 76.9) (-3.9, -1.4) (71.6, 79.2) (-6.5, 0.5) Median 76.5 -2.5 77.0 -3.0 Min 54.5 -21.0 61.5 -14.0 Max 96.5 17.0 85.5 10.0 Week 32 (Day 224) N 132 132 16 16 Mean 74.7 -3.5 73.6 -4.8 Std. Dev 8.09 7.84 7.88 9.56 95% CI (73.3, 76.1) (-4.8, -2.1) (69.4, 77.8) (-9.9, 0.3) Median 74.0 -3.0 73.8 -3.0 Min 57.5 -22.0 62.5 -24.0 Max 94.0 19.0 88.5 16.0










Week 36 (Day 252) N 132 132 15 15 Mean 73.9 -4.3 76.3 -2.5 Std. Dev 6.94 6.50 6.53 6.20 95% CI (72.7, 75.1) (-5.4, -3.2) (72.7, 80.0) (-5.9, 1.0) Median 73.5 -4.5 76.5 -1.0 Min 53.0 -20.0 66.0 -14.5 Max 89.0 13.0 85.5 4.5 Week 40 (Day 280) N 132 132 15 15 Mean 75.0 -3.2 77.6 -1.2 Std. Dev 7.57 6.90 9.30 8.53 95% CI (73.7, 76.3) (-4.4, -2.0) (72.4, 82.7) (-6.0, 3.5) Median 74.5 -3.3 78.5 -3.0 Min 51.0 -22.5 59.5 -15.5 Max 89.5 17.5 98.0 13.0 Week 44 (Day 308) N 130 130 15 15 Mean 75.7 -2.5 76.2 -2.6 Std. Dev 8.13 7.40 7.99 9.06 95% CI (74.3, 77.1) (-3.8, -1.2) (71.8, 80.6) (-7.6, 2.4) Median 75.8 -2.0 78.0 -3.5 Min 45.5 -19.5 63.5 -19.0 Max 96.0 15.0 88.5 15.0 Week 48 (Day 336) N 130 130 15 15 Mean 76.2 -2.0 78.1 -0.7 Std. Dev 7.09 7.52 6.87 5.18 95% CI (75.0, 77.4) (-3.3, -0.7) (74.3, 81.9) (-3.5, 2.2) Median 77.0 -1.5 78.5 -2.5 Min 61.0 -18.5 63.5 -7.5 Max 92.5 17.0 89.5 12.0 Week 52 (Day 364) N 129 129 15 15 Mean 77.6 -0.6 74.4 -4.4 Std. Dev 7.47 7.72 7.62 6.75 95% CI (76.3, 78.9) (-1.9, 0.8) (70.1, 78.6) (-8.2, -0.7) Median 77.5 -1.0 74.5 -4.0 Min 59.0 -20.0 60.0 -18.0 Max 97.5 18.0 85.0 7.5










Week 52 (LOCF) N 142 142 16 16 Mean 77.5 -0.6 75.3 -3.2 Std. Dev 7.60 7.68 8.16 8.29 95% CI (76.3, 78.8) (-1.8, 0.7) (70.9, 79.6) (-7.6, 1.3) Median 77.5 -1.0 75.8 -3.8 Min 59.0 -20.0 60.0 -18.0 Max 97.5 18.0 88.5 16.0 CI = confidence interval; LOCF = last observation carried forward; Min = minimum; Max = maximum; N = number of subjects; Std. Dev. = standard deviation. a. Subject population that is defined as the subject with both hypertension and hypercholesterolemia. b. Subject population that is defined as the subjects with both angina pectoris and hypercholesterolemia

including the subject with all of angina pectoris, hypertension and hypercholesterolemia. c. Baseline value for each subject is defined as the value of Week 0.

The mean percent change of LDL-C in the efficacy analysis set was decreased at Week 4 by about 10% from the baseline and then maintained that level until Week 52. In the evaluation of LDL-C by prior therapy for hypercholesterolemia, the mean percent change in LDL-C did not show significant changes throughout the 52 weeks in 116 subjects who received amlodipine/atorvastatin including the same dose of atorvastatin as that used during the screening period. There was only 1 subject who increased the dose of atorvastatin during the treatment period. Although appropriate evaluation is not possible because the number of subjects is small, the percent change from baseline at Week 4 was −23% in this subject. The effect continued until Week 24 and weakened at Week 52. The percent change from baseline was −9.5% at Week 52. The mean percent change in LDL-C in 40 subjects who did not receive prior therapy for hypercholesterolemia was decreased by 44.1% from baseline at Week 4 and the effect continued until Week 52 after that. By target disease, the mean percent change in LDL-C in subjects with hypertension and hypercholesterolemia showed similar changes as the efficacy analysis set. The mean percent change in LDL-C in subjects with all of angina pectoris, hypertension and hypercholesterolemia was −2.1% from baseline, which did not show significant changes by Week 24, but was decreased by 8.7% from baseline at Week 52. Out of 16 subjects with all of angina pectoris, hypertension and hypercholesterolemia, only 1 subject did not receive prior therapy for hypercholesterolemia. The other 15 subjects received the same dose of atorvastatin as that used during the screening period. For this reason, it was considered that no significant change was noted. A summary of actual value, change from baseline and percent change from baseline in LDL-C values at each visit (all subjects) is shown in Table 6.



Table 6. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - Low Density Lipoprotein Cholesterol (LDL-C) (mg/dL)


Amlodipine/Atorvastatin Actual Value Change From Baseline % Change From Baseline

Baselinea N 157 - - Mean 112.5 - - Std. Dev 38.32 - - 95% CI (106.5, 118.6) - - Median 103.0 - - Min 48.0 - - Max 211.0 - -

Week 4 (Day 28) N 157 157 157 Mean 93.0 -19.6 -10.9 Std. Dev 18.67 35.91 23.87 95% CI (90.0, 95.9) (-25.3, -13.9) (-14.6, -7.1) Median 92.0 -6.0 -6.7 Min 48.0 -122.0 -61.0 Max 141.0 34.0 38.2




Week 52 (LOCF) N 156 156 156 Mean 91.3 -21.0 -12.2 Std. Dev 18.18 35.75 23.55 95% CI (88.4, 94.2) (-26.7, -15.4) (-16.0, -8.5) Median 87.5 -7.0 -8.1 Min 44.0 -129.0 -61.2 Max 142.0 53.0 65.4



Table 6. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - Low Density Lipoprotein Cholesterol (LDL-C) (mg/dL)



CI = confidence interval; LOCF = last observation carried forward; Min = minimum; Max = maximum; N = number of subjects; Std. Dev. = standard deviation. a. Baseline value for each subject is defined as the value of Week 0.

Mean percent changes in TC and apolipoprotein B and mean changes of LDL-C/HDL-C and TC/HDL-C were decreased by Week 4, as observed for LDL-C, and the effect continued after that. The mean percent change in HDL-C showed a slightly increasing trend throughout the 52 weeks, except at Week 24 (1.5% to 4.0%). The mean percent change in TG also did not show significant changes throughout the 52 weeks (−5.0 to 0.2 mg/dL). A summary of actual value, change from baseline and percent change from baseline in lipid endpoints at each visit (all subjects) is shown in Table 7 (TC), Table 8 (HDL-C), Table 9 (TG), Table 10 (LDL-C/HDL-C), Table 11 (TC/HDL-C) and Table 12 (apolipoprotein B).



Table 7. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - Total Cholesterol (TC) (mg/dL)









CI = confidence interval; LOCF = last observation carried forward; Min = minimum; Max = maximum; N = number of subjects; Std. Dev. = standard deviation.



Table 7. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - Total Cholesterol (TC) (mg/dL)



a. Baseline value for each subject is defined as the value of Week 0.



Table 8. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - High Density Lipoprotein Cholesterol (HDL-C) (mg/dL)




Week 4 (Day 28) N 157 157 157 Mean 63.0 0.5 1.5 Std. Dev 14.25 7.09 10.63 95% CI (60.7, 65.2) (-0.7, 1.6) (-0.2, 3.2) Median 62.0 0.0 0.0 Min 33.0 -34.0 -34.0 Max 130.0 18.0 29.0

Week 12 (Day 84) N 156 156 156 Mean 64.4 2.0 4.0 Std. Dev 15.37 8.60 13.91 95% CI (62.0, 66.9) (0.6, 3.4) (1.8, 6.2) Median 64.5 1.5 2.5 Min 32.0 -25.0 -32.9 Max 132.0 32.0 60.0

Week 24 (Day 168) N 151 151 151 Mean 61.7 -0.9 -0.5 Std. Dev 14.72 8.68 13.26 95% CI (59.4, 64.1) (-2.2, 0.5) (-2.6, 1.6) Median 61.0 -1.0 -1.2 Min 30.0 -29.0 -34.2 Max 128.0 16.0 36.4

Week 52 (Day 364) N 145 145 145 Mean 64.0 1.1 2.2 Std. Dev 15.67 7.23 11.47 95% CI (61.5, 66.6) (-0.1, 2.3) (0.3, 4.0) Median 62.0 1.0 1.4 Min 36.0 -27.0 -31.0 Max 132.0 19.0 38.0

Week 52 (LOCF) N 157 157 157 Mean 63.7 1.2 2.5 Std. Dev 15.38 7.18 11.69 95% CI (61.2, 66.1) (0.0, 2.3) (0.6, 4.3) Median 61.0 1.0 1.4 Min 36.0 -27.0 -31.0 Max 132.0 19.0 38.0



Table 8. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - High Density Lipoprotein Cholesterol (HDL-C) (mg/dL)



CI = confidence interval; LOCF = last observation carried forward; Min = minimum; Max = maximum; N = number of subjects; Std. Dev. = standard deviation a. Baseline value for each subject is defined as the value of Week 0.



Table 9. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - Triglycerides (TG) (mg/dL)




Week 4 (Day 28) N 157 157 157 Mean 119.7 -0.6 8.2 Std. Dev 57.83 55.58 52.47 95% CI (110.6, 128.9) (-9.4, 8.1) (0.0, 16.5) Median 107.0 -2.0 -2.9 Min 40.0 -238.0 -67.4 Max 373.0 272.0 402.1

Week 12 (Day 84) N 156 156 156 Mean 115.3 -5.0 3.6 Std. Dev 66.51 65.70 49.94 95% CI (104.8, 125.8) (-15.4, 5.4) (-4.3, 11.5) Median 101.0 -8.0 -5.8 Min 34.0 -245.0 -69.4 Max 492.0 343.0 339.6

Week 24 (Day 168) N 151 151 151 Mean 117.8 -3.1 6.4 Std. Dev 62.46 64.63 45.75 95% CI (107.8, 127.9) (-13.5, 7.3) (-0.9, 13.8) Median 108.0 -3.0 -2.3 Min 35.0 -233.0 -71.6 Max 630.0 463.0 277.2

Week 52 (Day 364) N 145 145 145 Mean 121.2 0.2 8.5 Std. Dev 76.97 71.69 62.03 95% CI (108.6, 133.9) (-11.6, 12.0) (-1.6, 18.7) Median 106.0 -1.0 -1.0 Min 32.0 -180.0 -74.3 Max 696.0 595.0 589.1

Week 52 (LOCF) N 157 157 157 Mean 119.2 -1.2 7.2 Std. Dev 75.65 71.23 60.92 95% CI (107.3, 131.1) (-12.4, 10.1) (-2.4, 16.8) Median 103.0 -1.0 -1.2 Min 32.0 -180.0 -74.3 Max 696.0 595.0 589.1




Table 9. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - Triglycerides (TG) (mg/dL)






Table 10. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - Ratio of LDL-C/HDL-C


Amlodipine/Atorvastatin Actual Value Change From Baseline

Baselinea N 157 - Mean 1.9 - Std. Dev 0.85 - 95% CI (1.8, 2.1) - Median 1.7 - Min 0.5 - Max 4.2 -

Week 4 (Day 28) N 157 157 Mean 1.5 -0.4 Std. Dev 0.46 0.70 95% CI (1.5, 1.6) (-0.5, -0.3) Median 1.5 -0.1 Min 0.6 -2.3 Max 3.3 0.7




Week 52 (LOCF) N 156 156 Mean 1.5 -0.4 Std. Dev 0.47 0.68 95% CI (1.4, 1.6) (-0.5, -0.3) Median 1.5 -0.2 Min 0.5 -2.8 Max 3.1 0.8



Table 10. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - Ratio of LDL-C/HDL-C



CI = confidence interval; HDL-C = high density lipoprotein-C; LOCF = last observation carried forward; LDL-C = low density lipoprotein-C; Min = minimum; Max = maximum; N = number of subjects; Std. Dev. = standard deviation. a. Baseline value for each subject is defined as the value of Week 0.



Table 11. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - Ratio of TC/HDL-C



Baselinea N 157 - Mean 3.3 - Std. Dev 1.00 - 95% CI (3.2, 3.5) - Median 3.0 - Min 1.6 - Max 6.3 -





Week 52 (LOCF) N 157 157 Mean 2.9 -0.4 Std. Dev 0.61 0.77 95% CI (2.8, 3.0) (-0.6, -0.3) Median 2.8 -0.2 Min 1.6 -3.3 Max 5.2 1.2



Table 11. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - Ratio of TC/HDL-C



CI = confidence interval; HDL-C = high density lipoprotein-C; LOCF; = last observation carried forward; Min = minimum; Max = maximum; N = number of subjects; Std. Dev. = standard deviation; TC = total cholesterol. a. Baseline value for each subject is defined as the value of Week 0.



Table 12. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - Apolipoprotein B (mg/dL)












Table 12. Summary of Actual Value and Change From Baseline in Lipid Endpoints at Each Visit (All Subjects) - Apolipoprotein B (mg/dL)




Safety Results:

Treatment emergent adverse events (TEAEs) (all causality) reported for ≥2% of subjects overall are summarized in Table 13. The AEs were all mild or moderate in severity with the exception of 1 severe event (colitis ischemic). The incidence and severity of AEs by target disease did not show major differences.



Table 13. Treatment-Emergent Non Serious Adverse Events by System Organ Class and Preferred Term (All Causalities) for Events Having a Frequency Rate ≥2%

Number (%) of Subjects With Adverse Events by: System Organ Class

and MedDRA Preferred Term

Amlodipine/Atorvastatin n (%)

Number (%) of subjects: Evaluable for adverse events

159

Number (%) of subjects: With adverse events 101 (63.5)

Gastrointestinal disorders 16 (10.1) Abdominal discomfort 4 (2.5) Constipation 5 (3.1) Gastritis 4 (2.5) Gastrooesophageal reflux disease 5 (3.1)

Infections and infestations 77 (48.4) Bronchitis 11 (6.9) Cystitis 6 (3.8) Nasopharyngitis 53 (33.3) Pharyngitis 17 (10.7)

Injury, poisoning and procedural complications 9 (5.7) Fall 9 (5.7)

Musculoskeletal and connective tissue disorders 19 (11.9) Arthralgia 6 (3.8) Back pain 6 (3.8) Musculoskeletal stiffness 4 (2.5) Periarthritis 4 (2.5)

Nervous system disorders 6 (3.8) Headache 6 (3.8)

Respiratory, thoracic and mediastinal disorders 14 (8.8) Asthma 6 (3.8) Upper respiratory tract inflammation 8 (5.0)

Skin and subcutaneous tissue disorders 13 (8.2) Eczema 9 (5.7) Rash 4 (2.5)

Subjects are only counted once per treatment for each row. Includes all data collected since the first dose of study drug. MedDRA (v14.1) coding dictionary applied. MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects; v =version.

TEAEs (treatment-related) are summarized in Table 14. Treatment related AEs were all mild. Treatment related AEs reported in 2 or more subjects included only abdominal pain.



Table 14. Treatment-Emergent Adverse Events by MedDRA System Organ Class (Treatment Related)



Number (%) of subjects: Evaluable for adverse events 159

Number (%) of subjects: With adverse events 9 (5.7)

Eye disorders 1 (0.6) Gastrointestinal disorders 3 (1.9) General disorders and administration site conditions 1 (0.6) Neoplasms benign, malignant and unspecified (including cyst and polyps) 1 (0.6) Nervous system disorders 1 (0.6) Psychiatric disorders 1 (0.6) Reproductive system and breast disorders 1 (0.6) Skin and subcutaneous tissue disorders 2 (1.3) Subjects are only counted once per treatment for each row. Includes all data collected since the first dose of study drug. MedDRA (v14.1) coding dictionary applied. MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects; v =version.

SAEs are summarized in Table 15. SAEs were noted in 11 subjects (6.9%) among all subjects, but a causal relationship to the study drug was ruled out in all the subjects.



Table 15. Treatment-Emergent Serious Adverse Events by System Organ Class and Preferred Term (All Causalities)


and MedDRA Preferred Term


Number (%) of subjects: Evaluable for adverse events

159

Number (%) of subjects: With adverse events

11 (6.9)

Cardiac disorders 2 (1.3) Atrial fibrillation 1 (0.6) Atrioventricular block complete 1 (0.6)

Gastrointestinal disorders 2 (1.3) Colitis ischaemic 1 (0.6) Colonic polyp 1 (0.6)

Hepatobiliary disorders 1 (0.6) Cholecystitis acute 1 (0.6)

Injury poisoning and procedural complications 2 (1.3) Humerus fracture 1 (0.6) Thoracic vertebral fracture 1 (0.6)

Neoplasms benign, malignant and unspecified (including cyst and polyps) 4 (2.5) Benign soft tissue neoplasm 1 (0.6) Breast cancer 1 (0.6) Carcinoid tumour of the gastrointestinal tract 1 (0.6) Colon adenoma 1 (0.6) Rectal neoplasm 1 (0.6)

Vascular disorders 1 (0.6) Aortic aneurysm 1 (0.6)

Subjects are only counted once per treatment for each row. Includes all data collected since the first dose of study drug. MedDRA (v14.1) coding dictionary applied. MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects; v =version.

Permanent Discontinuations due to AEs: Discontinuations due to AEs are summarized in Table 16. The study treatment was discontinued due to AEs in 8 subjects. Among these AEs, 3 events in 3 of the 8 subjects were assessed as related to the study drug. These 3 AEs were not serious and were all mild in severity.



Table 16. Discontinuations From Treatment Due to Adverse Events

Serial No.

System Organ Class

MedDRA Preferred Term

Treatment Phase

Treatment at Onset Study Start Daya

/Study Stop Daya

Severity/ Outcome

Action/Causality SAE

1 Gastrointestinal disorders

Colonic polypb Active Amlodipine/Atorvastatin 164/ (>225)

Moderate/Still present

Study drug action: (Permanently discontinued)

Subject action: (D/C study)/Other -

unknown but not related to study drug

Yes

Neoplasms benign,

malignant and unspecified

(including cyst and polyps)

Carcinoid tumour of the gastrointestinal

tractb

Active Amlodipine/Atorvastatin 164/ (>225)





Yes

Neoplasm benign,

malignant and unspecified

(including cyst and polyps)

Colon adenomab Active Amlodipine/Atorvastatin 164/ (>225)





Yes

2 Cardiac disorders

Atrial fibrillationb Active Amlodipine/Atorvastatin 64/ (>64)

Mild/Still present



because there is no change in before the start of the study and

the use medicine

Yes




Serial No.

System Organ Class


Treatment Phase


/Study Stop Daya

Severity/ Outcome


3 Nervous system

disorders

Headacheb Active Amlodipine/Atorvastatin 19/21 Mild/Resolved Study drug action: (Permanently discontinued)

Subject action: (D/C study)/Study drug

No

4 Skin and subcutaneous

tissue disorders

Eczemab Active Amlodipine/Atorvastatin 96/(>103) Mild/Still present


Subject action: (Treatment given, D/C study)/Study

drug

No

5 Cardiac disorders

Atrioventricular block completeb

Active Amlodipine/Atorvastatin 110/(>120) Mild/Still present



because there was no change in the

medicine used later ahead in the start of

the study

Yes

6 Injury, poisoning and

procedural complications

Thoracic vertebral fractureb

Active Amlodipine/Atorvastatin 246/(>253) Moderate/Still present


Subject action: (Treatment given, D/C study)/Other -

traffic accident

Yes




Serial No.

System Organ Class


Treatment Phase


/Study Stop Daya

Severity/ Outcome


7 Investigations Alanine aminotransferase

increasedb

Active Amlodipine/Atorvastatin 85/(>135) Mild/Still present


Subject action: (D/C study)/Other illness -

gall stone disease

No

8 Skin and subcutaneous

tissue disorders

Rashb Active Amlodipine/Atorvastatin 140/(>168) Mild/Still present


Subject action: (Treatment given, D/C study)/Study

drug

No

() Values in brackets were imputed from incomplete dates and times. SAE = Serious Adverse Event (according to Investigators assessment). Treatment column gives study treatment at time of adverse event. MedDRA (v14.1) coding dictionary applied. a. Day relative to start of study treatment. First day of study treatment = Day 1. b. Treatment emergent.



Dose reduction or Temporary Discontinuation due to AEs: The study treatment was temporarily discontinued due to AEs in 2 subjects, but a causal relationship to the study drug was ruled out in both subjects. There were no dose reductions due to AEs.

Deaths: Deaths due to AEs were not reported in this study.

Common laboratory test abnormalities were urinary occult blood (positive) and gamma-glutamyl transpeptidase increased. Adverse events related to laboratory data were mild or moderate in severity, and a causal relationship to the study drug was ruled out for all the events. Vital signs also did not show apparent changes throughout the 52 weeks. On electrocardiograms, 2 AEs (atrial fibrillation and atrioventricular block complete) in 2 subjects were assessed as serious, and the study treatment was discontinued, although these events were mild in severity and a causal relationship to the study drug was ruled out for both. In 1 of these subjects the event improved, and in the other subject the event resolved. None of the subjects with concurrent angina pectoris were diagnosed with worsening symptoms of angina pectoris.

CONCLUSIONS: In this study, amlodipine/atorvastatin combination tablets were administered for 52 weeks to subjects with both hypertension and hypercholesterolemia, or with both angina pectoris and hypercholesterolemia. The results obtained in the study are shown below.

• Deaths due to AEs were not reported in this study. For all SAEs, a causal relationship to study drug was ruled out. All causality AEs were all mild or moderate in severity, with the exception of 1 severe event (ischemic colitis). Treatment related AEs were all mild, and AEs reported in 2 or more subjects included only abdominal pain.

• The mean values of SBP and DBP generally changed to below baseline and were well-controlled throughout the study period regardless of the presence/absence of angina pectoris.

• In the mean percent change compared to the baseline at each time point, LDL-C decreased by about 10% until Week 4 and maintained that level by Week 52. When evaluated by the prior therapy for hypercholesterolemia, the mean percent change of LDL-C did not show significant changes throughout the 52 weeks in 116 subjects who received amlodipine/atorvastatin including the same dose of atorvastatin as that used during the screening period. Only 1 subject received an increase of the dose of atorvastatin during the treatment period and the decrease of the mean percent change of LDL-C was observed for the subject. The mean percent change in LDL-C decreased very effectively in 40 subjects who did not receive prior therapy for hypercholesterolemia.

• Regarding lipid endpoints other than LDL-C, mean percent changes in TC and apolipoprotein B and mean changes of LDL-C/HDL-C and TC/HDL-C were decreased by Week 4, consistent with those for LDL-C, and the effect continued after that. The mean percent change in HDL-C showed a slightly increasing trend throughout the



52 weeks except at Week 24. The mean change in TG also did not show significant changes throughout the 52 weeks.

The above results showed that the safety of study drug in subjects with the target diseases of this study was satisfactory. With regard to efficacy, blood pressure was controlled by amlodipine/atorvastatin throughout the study period, and hyperlipidemia improved in subjects who had not received prior therapy, and was well-controlled in subjects who had received prior therapy.


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