Multiple Ascending Dose and DDI Study

Phase 1CompletedNCT03031119

Pfizer62 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

62

Conditions

Healthy Volunteers

Interventions

Tablets administered once or twice daily, with food, in Part A.

PF-06835919DRUG

Tablets administered once or twice daily, with food, in Part A. Tablets administered once or twice daily, with food and atorvastatin in Part B.

atorvastatinDRUG

In Part B, tablets administered once or twice daily, with food, with and without PF-06835919.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Locations (1)

Pfizer Clinical Research Unit

Brussels, Belgium

Outcomes

Primary Outcomes

Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)

Part A

Time frame: Screening to Day 24

Number of Participants With Clinical Laboratory Abnormalities

Part A

Time frame: Day -2 to Day 24

Change from baseline in vital signs

Part A

Time frame: Day -1 to Day 24

Change from baseline in 12-lead electrocardiogram

Part A

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose

Data from ClinicalTrials.gov

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Secondary Outcomes

Maximum Observed Plasma Concentration (Cmax) on Day 1 Part A

Time frame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose

Maximum Observed Plasma Concentration (Cmax) on Day 7 Part A

Time frame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose

Maximum Observed Plasma Concentration (Cmax) on Day 14 Part A

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose

Apparent Oral Clearance (CL/F) on Day 14 Part A

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose

Accumulation Ratio (Rac) on Day 14 Part A

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Screening to Day 18

Number of Participants With Clinical Laboratory Abnormalities

Part B

Time frame: Day -2 to Day 18

Change from Baseline in Vital Signs

Part B

Time frame: Day -2 to Day 18

Change from baseline in 12-lead electrocardiogram

Part B

Time frame: Day -2 to Day 18

Area Under the Curve from Time Zero to end of dosing interval (AUCtau) on Day 7 Part A

Time frame: 0,0.5,1,2,4,5,6,8 and 12 hours post-dose

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