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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT02211261
First received: August 6, 2014
Last updated: May 8, 2017
Last verified: May 2017
  Purpose
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 Intervention Phase
Type 2 Diabetes Mellitus Biological: PF-06293620 Biological: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
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

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number and Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) - Single Ascending Dose Cohorts (SAD) [ Time Frame: Between days -1 to 85 ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 85 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

  • Number and Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) related to drug treatment- Single Ascending Dose Cohorts (SAD) [ Time Frame: Between days -1 and 85 ]
    An AE was any untoward medical occurrence in a participant who received study drug with the possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment related AEs are events between first dose of study drug and up to 85 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

  • Number of participants with dose limiting or intolerable adverse events - SAD Cohorts [ Time Frame: Between days -1 and 85 ]
    Dose-limiting or intolerable toxicities defined by common terminology criteria for adverse events (CTCAE) in 2 or more subjects per treatment arm

  • Incidence of immunogenicity - SAD Cohorts [ Time Frame: Day -1, 15, 29, 57 and 85 ]
    presence of anti-drug antibodies

  • Number and Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) - Multiple Ascending Dose Cohorts (MAD) [ Time Frame: Between days -1 to 169 ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 85 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

  • Number and Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) related to drug treatment- Multiple Ascending Dose Cohorts (MAD) [ Time Frame: Between days -1 and 169 ]
    An AE was any untoward medical occurrence in a participant who received study drug with the possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment related AEs are events between first dose of study drug and up to 85 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

  • Number of participants with dose limiting or intolerable adverse events - MAD Cohorts [ Time Frame: Between days -1 and 169 ]
    Dose-limiting or intolerable toxicities defined by common terminology criteria for adverse events (CTCAE) in 2 or more subjects per treatment arm

  • Incidence of immunogenicity - MAD Cohorts [ Time Frame: Day -1, 15, 29, 57, 85, 113, 141 and 169 ]
    presence of anti-drug antibodies


Secondary Outcome Measures:
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) - SAD Cohorts [ Time Frame: Days 1-15,22,29,43,57 and 85 ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 85)] - SAD Cohorts [ Time Frame: Days 1-15,22,29,43,57 and 85 ]
    AUC (0 - 85)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 85). It is obtained from AUC (0 - t) plus AUC (t - 8).

  • Systemic Clearance (CL) - SAD Cohorts [ Time Frame: Days 1-15,22,29,43,57, and 8 ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body.

  • Apparent Oral Clearance (CL/F) - SAD Cohorts [ Time Frame: Days 1-15,22,29,43,57 and 85 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  • Maximum Observed Plasma Concentration (Cmax)-SAD Cohorts [ Time Frame: Days 1-15,22,29,43,57 and 85 ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax)- SAD Cohorts [ Time Frame: Days 1-15,22,29,43,57 and 85 ]
  • Apparent Volume of Distribution (Vz/F)- SAD Cohorts [ Time Frame: Days 1-15,22,29,43,57 and 85 ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

  • Plasma Decay Half-Life (t1/2)- SAD Cohorts [ Time Frame: Days 1-15,22,29,43,57 and 85 ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) - MAD Cohorts [ Time Frame: Days 1-15,22,27, 28,29,43,57,58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141 and 169 ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 85)] - MAD Cohorts [ Time Frame: Days 1-15,22,27, 28,29,43,57,58, 59, 63, 64, 71, 78, 84 and 85 ]
    AUC (0 - 85)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 85). It is obtained from AUC (0 - t) plus AUC (t - 8).

  • Systemic Clearance (CL) - MAD Cohorts [ Time Frame: Days 1-15,22,27,28,29,43,57,58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141 and 169 ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body.

  • Apparent Oral Clearance (CL/F) - MAD Cohorts [ Time Frame: Days 1-15,22,27, 28,29,43,57,58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141 and 169 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  • Maximum Observed Plasma Concentration (Cmax)-MAD Cohorts [ Time Frame: Days 1-15,22,27, 28,29,43,57,58, 59, 63, 64, 71, 78, 84, and 85 ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax)- MAD Cohorts [ Time Frame: Days 1-15,22,27, 28,29,43,57,58, 59, 63, 64, 71, 78, 84 and 85 ]
  • Apparent Volume of Distribution (Vz/F)- MAD Cohorts [ Time Frame: Days 1-15,22,27, 28,29,43,57,58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141 and 169 ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

  • Plasma Decay Half-Life (t1/2)- MAD Cohorts [ Time Frame: Days 1-15,22,27, 28,29,43,57,58, 59, 63, 64, 71, 78, 84, 85 ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.


Enrollment: 84
Actual Study Start Date: September 2014
Study Completion Date: January 2017
Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02211261

Locations
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
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02211261     History of Changes
Other Study ID Numbers: B3501001
Study First Received: August 6, 2014
Last Updated: May 8, 2017

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

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

ClinicalTrials.gov processed this record on September 19, 2017