Clinical trial NCT02211261: A Phase 1 Single/Multiple Dose Study Of PF-06293620 To Assess Safety, Tolerability And Pharmacokinetics In Subjects With Type 2 Diabetes Mellitus
Official title: A Phase 1 Double-blind, Placebo-controlled, Randomized, Single- And Multiple-ascending Dose Study To Assess The Safety, Tolerability, And Pharmacokinetics Of Pf-06293620 In Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Keywords: first in human
single dose
multiple dose
escalation
safety study
Type 2 Diabetes Mellitus
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-08-07
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: A first in human study to determine the safety, tolerability and pharmacokinetics of single and multiple ascending doses of PF-06293620 in subjects with Type 2 Diabetes Mellitus


Eligibility criteria: Inclusion Criteria:

* Men and women of non-childbearing potential with Type 2 Diabetes Mellitus
* Subjects on stable doses of metformin \>/= 1500 mg daily (SAD cohorts) or \>/= 1000 mg daily (MAD cohorts) x 30 days prior to screening
* HbA1c 7-10% (SAD Cohorts) or 6.5-10% (MAD cohorts) inclusive at screening
* Fasting C-peptide \>1.12 ng/mL (SAD cohorts) or \>/= 0.8 mg/mL (MAD cohorts) at screening

Exclusion Criteria:

* History of Type 1 diabetes mellitus
* Evidence of diabetic complications with significant end-organ damage
* History of chronic pancreatitis or at high risk for pancreatitis
* Poorly controlled hypertension
* History of cardiovascular or cerebrovascular event or procedure

Primary outcomes:
measure: Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events
timeFrame: Days 1 to 85 for SAD cohorts and Days 1 to 169 for MAD cohorts; participants with positive anti-drug antibody (ADA) results were followed up to stabilization of ADA titers or up to 9 months after Day 169 visit.
measure: Number of Participants With Dose Limiting or Intolerable Adverse Events
timeFrame: Days 1 to 85 for SAD cohorts; Days 1 to 169 for MAD Cohorts
measure: Number of Participants With Positive Anti-drug Antibody (ADA) Result
timeFrame: Days 1 to 85 for SAD cohorts; Days 1 to 169 for MAD Cohorts
Secondary outcomes:
measure: Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06293620 (SAD Cohorts)
timeFrame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
measure: Dose-normalized AUCinf (AUCinf(dn)) of PF-06293620 (SAD Cohorts)
timeFrame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
measure: Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06293620 (SAD Cohorts)
timeFrame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
measure: Dose-normalized AUClast (AUClast(dn)) of PF-06293620 (SAD Cohorts)
timeFrame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
measure: Clearance (CL) of PF-06293620 (SAD Cohorts)
timeFrame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
measure: Apparent Clearance (CL/F) of PF-06293620 (SAD Cohorts)
timeFrame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
measure: Maximum Serum Concentration (Cmax) of PF-06293620 (SAD Cohorts)
timeFrame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
measure: Time for Maximum Serum Concentration (Tmax) of PF-06293620 (SAD Cohorts)
timeFrame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
measure: Steady-state Volume of Distribution (Vss) of PF-06293620 (SAD Cohorts)
timeFrame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
measure: Apparent Volume of Distribution (Vz/F) of PF-06293620 (SAD Cohorts)
timeFrame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
measure: Terminal Elimination Half-life (Thalf) of PF-06293620 (SAD Cohorts)
timeFrame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
measure: Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration
timeFrame: Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
measure: Maximum Serum Concentration (Cmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration
timeFrame: Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
measure: Average Concentration (Cav) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration
timeFrame: Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
measure: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06293620 (MAD Cohorts) After Day 57 Administration
timeFrame: Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
measure: Time for Maximum Serum Concentration (Tmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration
timeFrame: Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
measure: Apparent Clearance (CL/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration
timeFrame: Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
measure: Apparent Volume of Distribution (Vz/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration
timeFrame: Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
measure: Terminal Elimination Half-life (Thalf) of PF-06293620 (MAD Cohorts) After Day 57 Administration
timeFrame: Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
measure: Observed Accumulation Ratio Based on AUC (Rac) of PF-06293620 (MAD Cohorts)
timeFrame: Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
measure: Observed Accumulation Ratio Based on Cmax (Rac,Cmax) of PF-06293620 (MAD Cohorts)
timeFrame: Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research, Inc.
state: California
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research, Incorporated
state: California
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: South Miami
country: United States
facility: Qps Mra, Llc
state: Florida
city: South Miami
country: United States
facility: Qps-Mra Llc
state: Florida
city: High Point
country: United States
facility: High Point Clinical Trials Center, LLC
state: North Carolina
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: