Multiple Ascending Dose and DDI Study

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)

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: PF-06835919; Drug: atorvastatin

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, B-1070
    • Pfizer Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Tablets administered once or twice daily, with food, in Part A for 14 days.	Drug: Placebo; Tablets administered once or twice daily, with food, in Part A.
Experimental: PF-06835919; 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; Tablets administered once or twice daily, with food, in Part A. Tablets administered once or twice daily, with food and atorvastatin in Part B.; Drug: atorvastatin; In Part B, tablets administered once or twice daily, with food, with and without PF-06835919.
Experimental: atorvastatin; 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; Tablets administered once or twice daily, with food, in Part A. Tablets administered once or twice daily, with food and atorvastatin in Part B.; Drug: atorvastatin; In Part B, tablets administered once or twice daily, with food, with and without PF-06835919.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: January 23, 2017
• First Submitted That Met QC Criteria: January 23, 2017
• First Posted (Estimate): January 25, 2017

Study Record Updates

• Last Update Posted (Actual): September 6, 2017
• Last Update Submitted That Met QC Criteria: September 5, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: nonalcoholic steatohepatitis
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: C1061002; 2016-004649-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No