Multiple Ascending Dose and DDI Study
Phase 1
Completed
- Conditions
- Healthy Volunteers
- Interventions
- Registration Number
- NCT03031119
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 62
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Tablets administered once or twice daily, with food, in Part A for 14 days. atorvastatin PF-06835919 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. PF-06835919 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. PF-06835919 atorvastatin 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. atorvastatin 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.
- Primary Outcome Measures
Name Time Method Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 3 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
Maximum Observed Plasma Concentration (Cmax) on Day 3 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
Number of Participants With Clinical Laboratory Abnormalities Day -2 to Day 24 Part A
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 7 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) Screening to Day 24 Part A
Change from baseline in 12-lead electrocardiogram Day -1 to Day 24 Part A
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) on Day 7 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day -1 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
Maximum Observed Plasma Concentration (Cmax) on Day 7 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
Plasma Decay Half-Life (t1/2) on Day 3 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
Change from baseline in vital signs Day -1 to Day 24 Part A
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) on Day -1 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day 3 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
Plasma Decay Half-Life (t1/2) on Day -1 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) on Day 3 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day 7 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
Maximum Observed Plasma Concentration (Cmax) on Day -1 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
Plasma Decay Half-Life (t1/2) on Day 7 of atorvastatin and 2 active metabolites 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose Part B
- Secondary Outcome Measures
Name Time Method 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 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 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 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 Maximum Observed Plasma Concentration (Cmax) 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 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 Maximum Observed Plasma Concentration (Cmax) 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 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 Change from Baseline in Vital Signs Day -2 to Day 18 Part B
Change from baseline in 12-lead electrocardiogram Day -2 to Day 18 Part B
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 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 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 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) Screening to Day 18 Part B
Number of Participants With Clinical Laboratory Abnormalities Day -2 to Day 18 Part B
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 Apparent Oral Clearance (CL/F) 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 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
Trial Locations
- Locations (1)
Pfizer Clinical Research Unit
🇧🇪Brussels, Belgium