Clinical trial NCT03031119: Multiple Ascending Dose and DDI Study
Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled Study To Assess Safety, Tolerability, And Pharmacokinetics Of Multiple Oral Doses Of Pf-06835919 In Healthy Adult Subjects (Part A); And An Open-label Study To Assess Multiple Oral Doses Of Pf-06835919 On Atorvastatin Pharmacokinetics (Part B)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: nonalcoholic steatohepatitis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-01-25
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Part A will investigate the safety, tolerability, PK and PD of PF-06835919 administered for 14 days in a multiple ascending dose design. Part B will assess the effect of PF-06835919 co-administration at low and high doses on the PK of atorvastatin in a single cohort.


Eligibility criteria: Inclusion Criteria:

* Healthy male and females (nonchildbearing potential)
* 18 to 55 years old
* Body Mass Index 17.5 to 30.5

Exclusion Criteria:

* Known hereditary fructose intolerance or fructose malabsorption disorder (Part A)
* Statin intolerance (Part B)
* Unable to consume high fructose syrup-containing beverage with each meal while in the unit (Part A)

Primary outcomes:
measure: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
timeFrame: Screening to Day 24
measure: Number of Participants With Clinical Laboratory Abnormalities
timeFrame: Day -2 to Day 24
measure: Change from baseline in vital signs
timeFrame: Day -1 to Day 24
measure: Change from baseline in 12-lead electrocardiogram
timeFrame: Day -1 to Day 24
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) on Day -1 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) on Day 3 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) on Day 7 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day -1 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day 3 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day 7 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 3 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 7 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
measure: Maximum Observed Plasma Concentration (Cmax) on Day -1 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
measure: Maximum Observed Plasma Concentration (Cmax) on Day 3 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
measure: Maximum Observed Plasma Concentration (Cmax) on Day 7 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
measure: Plasma Decay Half-Life (t1/2) on Day -1 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
measure: Plasma Decay Half-Life (t1/2) on Day 3 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
measure: Plasma Decay Half-Life (t1/2) on Day 7 of atorvastatin and 2 active metabolites
timeFrame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) on Day 1 Part A
timeFrame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) on Day 7 Part A
timeFrame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) on Day 14 Part A
timeFrame: 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48, and 72 hours post-dose
measure: Area Under the Curve from Time Zero to end of dosing interval (AUCtau) on Day 1 Part A
timeFrame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose
measure: Area Under the Curve from Time Zero to end of dosing interval (AUCtau) on Day 14 Part A
timeFrame: 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 Part A
timeFrame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 7 Part A
timeFrame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 14 Part A
timeFrame: 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose
measure: Apparent Oral Clearance (CL/F) on Day 7 Part A
timeFrame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose
measure: Apparent Oral Clearance (CL/F) on Day 14 Part A
timeFrame: 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose
measure: Minimum Observed Plasma Trough Concentration (Cmin) on Day 7 Part A
timeFrame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose
measure: Minimum Observed Plasma Trough Concentration (Cmin) on Day 14 Part A
timeFrame: 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose
measure: Accumulation Ratio (Rac) on Day 7 Part A
timeFrame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose
measure: Accumulation Ratio (Rac) on Day 14 Part A
timeFrame: 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose
measure: Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) on Day 7 Part A
timeFrame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose
measure: Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) on Day 14 Part A
timeFrame: 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose
measure: Plasma Decay Half-Life (t1/2) on Day 14 Part A
timeFrame: 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose
measure: Apparent Volume of Distribution (Vz/F) on Day 14 Part A
timeFrame: 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose
measure: Cumulative Amount of Drug Recovered Unchanged in Urine (Ae) on Day 14 Part A
timeFrame: 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose
measure: Percent Cumulative Amount of Drug Recovered Unchanged in Urine (Ae%) on Day 14 Part A
timeFrame: 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose
measure: Renal Clearance (CLr) on Day 14 Part A
timeFrame: 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose
measure: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
timeFrame: Screening to Day 18
measure: Number of Participants With Clinical Laboratory Abnormalities
timeFrame: Day -2 to Day 18
measure: Change from Baseline in Vital Signs
timeFrame: Day -2 to Day 18
measure: Change from baseline in 12-lead electrocardiogram
timeFrame: Day -2 to Day 18
measure: Area Under the Curve from Time Zero to end of dosing interval (AUCtau) on Day 7 Part A
timeFrame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: