Multiple Ascending Dose and DDI Study

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Placebo
* Drug: PF-06835919
* Drug: atorvastatin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Tablets administered once or twice daily, with food, in Part A for 14 days. | Drug: Placebo<br>* Tablets administered once or twice daily, with food, in Part A.<br>|
| Experimental: PF-06835919<br>Tablets administered once or twice daily, with food, in Part A for 14 days. Tablets administered once or twice daily, for 4 days at a low dose and for 4 days at a higher dose, with food and atorvastatin in Part B. | Drug: PF-06835919<br>* Tablets administered once or twice daily, with food, in Part A. Tablets administered once or twice daily, with food and atorvastatin in Part B.<br>Drug: atorvastatin<br>* In Part B, tablets administered once or twice daily, with food, with and without PF-06835919.<br>|
| Experimental: atorvastatin<br>In Part B, tablets administered once or twice daily, with food, with and without a low dose of PF-06835919 for 4 days and a higher dose of PF-06835919 for 4 days. | Drug: PF-06835919<br>* Tablets administered once or twice daily, with food, in Part A. Tablets administered once or twice daily, with food and atorvastatin in Part B.<br>Drug: atorvastatin<br>* In Part B, tablets administered once or twice daily, with food, with and without PF-06835919.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Part A | Screening to Day 24 | 
| Number of Participants With Clinical Laboratory Abnormalities | Part A | Day -2 to Day 24 | 
| Change from baseline in vital signs | Part A | Day -1 to Day 24 | 
| Change from baseline in 12-lead electrocardiogram | Part A | Day -1 to Day 24 | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) on Day -1 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) on Day 3 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) on Day 7 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day -1 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day 3 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day 7 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 3 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 7 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 
| Maximum Observed Plasma Concentration (Cmax) on Day -1 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 
| Maximum Observed Plasma Concentration (Cmax) on Day 3 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 
| Maximum Observed Plasma Concentration (Cmax) on Day 7 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 
| Plasma Decay Half-Life (t1/2) on Day -1 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 
| Plasma Decay Half-Life (t1/2) on Day 3 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 
| Plasma Decay Half-Life (t1/2) on Day 7 of atorvastatin and 2 active metabolites | Part B | 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) on Day 1 Part A |  | 0,0.5,1,2,4,5,6,8 and 12 hours post-dose | 
| Maximum Observed Plasma Concentration (Cmax) on Day 7 Part A |  | 0,0.5,1,2,4,5,6,8 and 12 hours post-dose | 
| Maximum Observed Plasma Concentration (Cmax) on Day 14 Part A |  | 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48, and 72 hours post-dose | 
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) on Day 1 Part A |  | 0,0.5,1,2,4,5,6,8 and 12 hours post-dose | 
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) on Day 14 Part A |  | 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 Part A |  | 0,0.5,1,2,4,5,6,8 and 12 hours post-dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 7 Part A |  | 0,0.5,1,2,4,5,6,8 and 12 hours post-dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 14 Part A |  | 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose | 
| Apparent Oral Clearance (CL/F) on Day 7 Part A |  | 0,0.5,1,2,4,5,6,8 and 12 hours post-dose | 
| Apparent Oral Clearance (CL/F) on Day 14 Part A |  | 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose | 
| Minimum Observed Plasma Trough Concentration (Cmin) on Day 7 Part A |  | 0,0.5,1,2,4,5,6,8 and 12 hours post-dose | 
| Minimum Observed Plasma Trough Concentration (Cmin) on Day 14 Part A |  | 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose | 
| Accumulation Ratio (Rac) on Day 7 Part A |  | 0,0.5,1,2,4,5,6,8 and 12 hours post-dose | 
| Accumulation Ratio (Rac) on Day 14 Part A |  | 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose | 
| Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) on Day 7 Part A |  | 0,0.5,1,2,4,5,6,8 and 12 hours post-dose | 
| Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) on Day 14 Part A |  | 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose | 
| Plasma Decay Half-Life (t1/2) on Day 14 Part A |  | 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose | 
| Apparent Volume of Distribution (Vz/F) on Day 14 Part A |  | 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose | 
| Cumulative Amount of Drug Recovered Unchanged in Urine (Ae) on Day 14 Part A |  | 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose | 
| Percent Cumulative Amount of Drug Recovered Unchanged in Urine (Ae%) on Day 14 Part A |  | 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose | 
| Renal Clearance (CLr) on Day 14 Part A |  | 0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose | 
| Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Part B | Screening to Day 18 | 
| Number of Participants With Clinical Laboratory Abnormalities | Part B | Day -2 to Day 18 | 
| Change from Baseline in Vital Signs | Part B | Day -2 to Day 18 | 
| Change from baseline in 12-lead electrocardiogram | Part B | Day -2 to Day 18 | 
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) on Day 7 Part A |  | 0,0.5,1,2,4,5,6,8 and 12 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nonalcoholic steatohepatitis