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A Phase 1 Single/Multiple Dose Study Of PF-06293620 To Assess Safety, Tolerability And Pharmacokinetics In Subjects With Type 2 Diabetes Mellitus

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ClinicalTrials.gov Identifier: NCT02211261
Recruitment Status : Completed
First Posted : August 7, 2014
Results First Posted : October 16, 2018
Last Update Posted : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

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

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Biological: PF-06293620 Biological: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
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
Actual Study Start Date : September 15, 2014
Actual Primary Completion Date : January 27, 2017
Actual Study Completion Date : January 27, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1-PF-06293620 or placebo
Single Ascending Dose PF-06293620 or placebo
Biological: PF-06293620
subcutaneous, single dose 0.3 mg/kg

Biological: Placebo
Subcutaneous normal saline single dose

Experimental: Cohort 2-PF-06293620 or placebo
Single Ascending Dose PF-06293620 or placebo
Biological: PF-06293620
Subcutaneous, single dose 1.0 mg/kg

Biological: Placebo
Subcutaneous normal saline single dose

Experimental: Cohort 3-PF-06293620 or placebo
Single Ascending Dose PF-06293620 or placebo
Biological: PF-06293620
Subcutaneous single dose 3 mg/kg

Biological: Placebo
Subcutaneous normal saline single dose

Experimental: Cohort 4-PF-06293620 or placebo
Single Ascending Dose PF-06293620 or placebo
Biological: PF-06293620
Subcutaneous single dose 6 mg/kg

Biological: Placebo
Subcutaneous normal saline single dose

Experimental: Cohort 5-PF-06293620 or placebo
Single Ascending Dose PF-06293620 or placebo
Biological: PF-06293620
Intravenous infusion single dose 1 mg/kg

Biological: Placebo
Intravenous infusion normal saline single dose

Experimental: Cohort 6-PF-06293620 or placebo
Multiple Ascending Dose PF-06293620 or placebo
Biological: PF-06293620
Subcutaneous injection multiple dose 75 mg (Days 1, 29 and 57)

Biological: Placebo
Subcutaneous injection normal saline multiple dose (Days 1, 29 and 57)

Experimental: Cohort 7 PF-06293620 or placebo
Multiple Ascending Dose PF-06293620 or placebo
Biological: PF-06293620
Subcutaneous injection multiple dose 150 mg (Days 1, 29 and 57)

Biological: Placebo
Subcutaneous injection normal saline multiple dose (Days 1, 29 and 57)

Experimental: Cohort 8-PF-06293620 or placebo
Multiple Ascending Dose PF-06293620 or placebo
Biological: PF-06293620
Subcutaneous injection multiple dose 250 mg (Days 1, 29 and 57)

Biological: Placebo
Subcutaneous injection normal saline multiple dose (Days 1, 29 and 57)

Experimental: Cohort 9-PF-06293620 or placebo
Multiple Ascending Dose PF-06293620 or placebo
Biological: PF-06293620
Subcutaneous injection multiple dose TBD mg (Days TBD)

Biological: Placebo
Subcutaneous injection normal saline multiple dose (Days TBD)




Primary Outcome Measures :
  1. Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events [ Time Frame: 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. ]
    An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of its causal relationship with study treatment. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; was life-threatening (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study drug and up to Day 85 (for SAD cohorts) or Day 169 (for MAD cohorts) that were absent before treatment or that worsened after treatment. AEs included both serious and non-serious AEs. Causality with the study treatment was determined by the investigator.

  2. Number of Participants With Dose Limiting or Intolerable Adverse Events [ Time Frame: Days 1 to 85 for SAD cohorts; Days 1 to 169 for MAD Cohorts ]
    Dose limiting or intolerable AEs were originally planned to be collected. However, this outcome measure was not actually summarized, since collection and monitoring of treatment-emergent AEs was performed during the study, and deemed sufficient to ensure the participants safety.

  3. Number of Participants With Positive Anti-drug Antibody (ADA) Result [ Time Frame: Days 1 to 85 for SAD cohorts; Days 1 to 169 for MAD Cohorts ]
    ADA against PF-06293620 in human serum samples was determined following a tiered approach using screening, confirmation, and titer/quantification by semi-quantitative enzyme linked immunosorbent assay (ELISA). Endpoint titer >=1.88 was considered positive.


Secondary Outcome Measures :
  1. Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06293620 (SAD Cohorts) [ Time Frame: 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 ]
    AUCinf was calculated as AUClast +(Clast*/kel), where AUClast is area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis, kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.

  2. Dose-normalized AUCinf (AUCinf(dn)) of PF-06293620 (SAD Cohorts) [ Time Frame: 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 ]
    AUCinf(dn) was calculated as AUCinf/dose, where AUCinf is area under the serum concentration-time profile from time 0 extrapolated to infinite time.

  3. Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06293620 (SAD Cohorts) [ Time Frame: 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 ]
    Area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) of PF-06293620 was determined using linear/log trapezoidal method.

  4. Dose-normalized AUClast (AUClast(dn)) of PF-06293620 (SAD Cohorts) [ Time Frame: 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 ]
    AUClast(dn) of PF-06293620 was calculated as AUClast/dose, where AUClast was area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration.

  5. Clearance (CL) of PF-06293620 (SAD Cohorts) [ Time Frame: 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 ]
    Clearance (CL) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to IV arms.

  6. Apparent Clearance (CL/F) of PF-06293620 (SAD Cohorts) [ Time Frame: 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 ]
    Apparent Clearance (CL/F) of PF-06293620 was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to SC arms.

  7. Maximum Serum Concentration (Cmax) of PF-06293620 (SAD Cohorts) [ Time Frame: 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 ]
    Maximum serum concentration (Cmax) of PF-06293620 was observed directly from data.

  8. Time for Maximum Serum Concentration (Tmax) of PF-06293620 (SAD Cohorts) [ Time Frame: 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 ]
    Time for Maximum serum concentration (Tmax) of PF-06293620 was observed directly from data as time of first occurrence.

  9. Steady-state Volume of Distribution (Vss) of PF-06293620 (SAD Cohorts) [ Time Frame: 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 ]
    Steady-state volume of distribution (Vss) of PF-06293620 was calculated as CL*MRT, where MRT was the mean residence time calculated as (AUMCinf/AUCinf - infusion duration/2), AUMCinf was area under the moment curve from time 0 extrapolated to infinity; CL was the clearance. This outcome measure only applies to IV arms.

  10. Apparent Volume of Distribution (Vz/F) of PF-06293620 (SAD Cohorts) [ Time Frame: 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 ]
    Apparent Volume of Distribution (Vz/F) of PF-06293620 was calculated as dose/(AUCinf*kel), where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time, kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. This outcome measure only applies to SC arms.

  11. Terminal Elimination Half-life (Thalf) of PF-06293620 (SAD Cohorts) [ Time Frame: 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 ]
    Terminal elimination half-life (Thalf) of PF-06293620 was calculated as ln(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.

  12. 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 [ Time Frame: 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 ]
    Tau refers to the dosing interval, which was 4 weeks (672 hours). Area under the concentration-time profile from time 0 to time tau (AUCtau) was determined using linear/log trapezoidal method.

  13. Maximum Serum Concentration (Cmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration [ Time Frame: 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 ]
  14. Average Concentration (Cav) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration [ Time Frame: 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 ]
    Average Concentration (Cav) of PF-06293620 was calculated as AUCtau/tau, where AUCtau was area under the concentration-time profile from time 0 to time tau, and tau was the dosing interval, 4 weeks (672 hours).

  15. Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06293620 (MAD Cohorts) After Day 57 Administration [ Time Frame: Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 ]
  16. Time for Maximum Serum Concentration (Tmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration [ Time Frame: 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 ]
    Time for maximum serum concentration (Tmax) of PF-06293620 was observed directly from data as time of first occurrence.

  17. Apparent Clearance (CL/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration [ Time Frame: Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 ]
    Apparent clearance (CL/F) of PF-06293620 was calculated as dose/AUCtau, where AUCtau was area under the concentration-time profile from time 0 to time tau, and tau was the dosing interval, 4 weeks (672 hours).

  18. Apparent Volume of Distribution (Vz/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration [ Time Frame: Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 ]
    Apparent volume of distribution (Vz/F) of PF-06293620 was calculated as dose/(AUCtau/kel), where AUCtau was area under the concentration-time profile from time 0 to time tau, and tau was the dosing interval, 4 weeks (672 hours); and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.

  19. Terminal Elimination Half-life (Thalf) of PF-06293620 (MAD Cohorts) After Day 57 Administration [ Time Frame: Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 ]
    Terminal elimination half-life (Thalf) of PF-06293620 was calculated as ln(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.

  20. Observed Accumulation Ratio Based on AUC (Rac) of PF-06293620 (MAD Cohorts) [ Time Frame: 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 ]
    Observed accumulation ratio based on AUC (Rac) of PF-06293620 was calculated as AUCtau(Day57)/AUCtau(Day1).

  21. Observed Accumulation Ratio Based on Cmax (Rac,Cmax) of PF-06293620 (MAD Cohorts) [ Time Frame: 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 ]
    Observed accumulation ratio based on Cmax (Rac,Cmax) of PF-06293620 was calculated as Cmax(Day57)/Cmax(Day1).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02211261


Locations
Layout table for location information
United States, California
Profil Institute for Clinical Research, Inc.
Chula Vista, California, United States, 91911
Profil Institute for Clinical Research, Incorporated
Chula Vista, California, United States, 91911
United States, Florida
Avail Clinical Research, LLC
DeLand, Florida, United States, 32720
Orlando Clinical Research Center
Orlando, Florida, United States, 32809
Qps Mra, Llc
South Miami, Florida, United States, 33143
Qps-Mra Llc
South Miami, Florida, United States, 33143
United States, North Carolina
High Point Clinical Trials Center, LLC
High Point, North Carolina, United States, 27265
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] October 2, 2015
Statistical Analysis Plan  [PDF] November 8, 2016


Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02211261     History of Changes
Other Study ID Numbers: B3501001
First Posted: August 7, 2014    Key Record Dates
Results First Posted: October 16, 2018
Last Update Posted: October 16, 2018
Last Verified: October 2018

Keywords provided by Pfizer:
first in human
single dose
multiple dose
escalation
safety study
Type 2 Diabetes Mellitus

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases