A PHASE 2A, 2-PART, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY PLACEBO-CONTROLLED, PARALLEL-GROUP (SPONSOR OPEN) STUDY TO ASSESS PHARMACODYNAMICS AND SAFETY OF PF-06865571 (DGAT2I) COADMINISTERED WITH PF-05221304 (ACCI) IN ADULT PARTICIPANTS WITH PRESUMED NONALCOHOLIC STEATOHEPATITIS (NASH)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 75
- 试验地点
- 19
- 主要终点
- Percent Change From Baseline (CFB) in Percent (%) Liver Fat as Assessed Via Magnetic Resonance Imaging Using Proton Density Fat Fraction Acquisition (MRI-PDFF) at Week 6
研究概览
简要总结
The study will evaluate the effect of coadministration of a range of doses of DGAT2i with 1 dose of ACCi, on hepatic steatosis and the ability of DGAT2i to mitigate ACCi-induced elevations in serum triglycerides. The study has a 2-part design with sequential conduct of Part 1 and Part 2 with each part conducted in distinct/separate cohorts of participants. The overall study design, objectives/endpoints, eligibility criteria for both parts is envisioned to be identical, however, data from Part 1 will be used to determine whether to conduct Part 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind, Double-dummy, Placebo controlled
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BMI ≥25 and ≤ 40 kg/m2
- •concomitant medical conditions associated with NAFLD
排除标准
- •Evidence of other causes of liver disease such as Alcoholic steatohepatitis, (de)compensated cirrhosis, active viral hepatitis
- •Any condition possibly affecting drug absorption
- •Unstable liver function tests
- •Recent cardiovascular event(s),
- •Malignancies
研究组 & 干预措施
Placebo
Participants will receive medication for 6 weeks
干预措施: Placebo (Drug)
DGAT2i (100 mg BID) + ACCi (10 mg BID)
Participants will receive medication for 6 weeks
干预措施: PF-05221304 (Drug)
DGAT2i (25 mg BID) + ACCi (10 mg BID)
Participants will receive medication for 6 weeks
干预措施: PF-06865571 (Drug)
DGAT2i (25 mg BID) + ACCi (10 mg BID)
Participants will receive medication for 6 weeks
干预措施: PF-05221304 (Drug)
DGAT2i (100 mg BID) + ACCi (10 mg BID)
Participants will receive medication for 6 weeks
干预措施: PF-06865571 (Drug)
DGAT2i (300 mg QD) + ACCi (20 mg QD)
Participants will receive medication for 6 weeks
干预措施: PF-06865571 (Drug)
DGAT2i (300 mg QD) + ACCi (20 mg QD)
Participants will receive medication for 6 weeks
干预措施: PF-05221304 (Drug)
DGAT2i (300 mg BID) + ACCi (10 mg BID)
Participants will receive medication for 6 weeks
干预措施: PF-06865571 (Drug)
DGAT2i (300 mg BID) + ACCi (10 mg BID)
Participants will receive medication for 6 weeks
干预措施: PF-05221304 (Drug)
结局指标
主要结局
Percent Change From Baseline (CFB) in Percent (%) Liver Fat as Assessed Via Magnetic Resonance Imaging Using Proton Density Fat Fraction Acquisition (MRI-PDFF) at Week 6
时间窗: Baseline, Week 6
MRI-PDFF technique is an established method that enables quantification of fat content in the liver. It measures the fraction of mobile protons in the liver attributable to fat content and provides whole liver coverage so that fat content can be assessed across 8 Couinaud liver segments. Whole liver PDFF = the sum of PDFFs for (Segment I + Segment II + Segment III + Segment IVa + Segment IVb + Segment V + Segment VI + Segment VII + Segment VIII) divided by (number of segments assessed and no missing/mapping at Baseline, and on Week 6). If some segments did not have results reported at Baseline and/or Week 6, liver PDFF was to be calculated using data in segments that had data available at both Baseline visit and Week 6 visit. For this outcome measure (OM), baseline is defined as the assessment undertaken between Visit 3/Week -2 and Visit 4/Day 1.
次要结局
- Number of Participants With TEAEs of Special Interest by Preferred Term (PT)(Baseline up to at least 28 days after the last administration of the study intervention or until study completion or withdrawal, whichever was longer (maximum of approximately 24 weeks).)
- Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality(From baseline to end of follow-up or until study discontinuation/withdrawal, whichever was longer (maximum of approximately 19 weeks))
- Percent CFB in Fasting Serum Triglycerides at Week 6(Baseline, Week 6)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Baseline up to at least 28 days after the last administration of the study intervention or until study completion or withdrawal, whichever was longer (maximum of approximately 24 weeks).)
- Number of Participants With Abnormalities in Laboratory Parameters of Special Interest Meeting Pre-Defined Criteria(From baseline to end of follow-up or until study discontinuation/withdrawal, whichever was longer (maximum of approximately 19 weeks))
- Number of Participants With Post-Baseline Vital Signs Data Meeting Pre-Defined Criteria(Baseline, Week 6, the first follow-up visit (Week 8), and the date of discontinuation/withdrawal from study (maximum of approximately 12 weeks after Day 1) if applicable)
- Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Pre-Defined Criteria(Baseline, Week 6, the first follow-up visit (Week 8), and the date of discontinuation/withdrawal from study (maximum of approximately 12 weeks after Day 1) if applicable)