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Safety and Tolerability of Ascending Intravenous Doses of PF-05231023 In Adult Subjects With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01396187
First received: July 6, 2011
Last updated: December 30, 2014
Last verified: December 2014
  Purpose

This is a trial in subjects with Type 2 diabetes mellitus to study the safety, tolerability and pharmacokinetics of multiple ascending doses of PF-05231023.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: PF-05231023
Other: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Placebo-Controlled Randomized Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Ascending Intravenous Doses Of PF-05231023 In Adult Subjects With Type 2 Diabetes Mellitus

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With Abnormal Physical Examination Findings [ Time Frame: Baseline up to Day 42 ] [ Designated as safety issue: Yes ]
    Physical examination included assessment of height, weight, blood pressure, pulse rate and body temperature. Criteria for abnormal physical findings was based on investigator's discretion and were reported as adverse event (AE), as planned.

  • Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Day 77 ] [ Designated as safety issue: Yes ]
    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 Day 77 which were absent before treatment or that worsened relative to pretreatment state.

  • Number of Participants With Abnormal Laboratory Values [ Time Frame: Baseline up to Day 42 ] [ Designated as safety issue: Yes ]
    Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit and red blood cells (RBCs)(less than [<] 0.8*lower limit of normal[LLN]); leucocytes (<0.6/greater than [>]1.5*upper limit of normal [ULN]); platelets (<0.5*LLN></0>1.75*ULN); neutrophils, lymphocytes (<0.8*LLN></0>1.2*ULN); eosinophils, basophils, monocytes (>1.2*ULN); total bilirubin, direct bilirubin, indirect bilirubin (>1.5*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (>3*ULN), total protein, albumin (<0.8*LLN></0>1.2*ULN); creatinine, urea (>1.3*ULN); glucose (<0.6*LLN></0>1.5*ULN); uric acid (>1.2*ULN); sodium, potassium, chloride, calcium, bicarbonate (<0.9*LLN></0>1.1*ULN); urine RBCs, urine white blood cells (WBCs) (> or equal[=]20 high-powered field), urine bacteria >20 high-powered field. Total number of participants with any laboratory abnormalities were reported.

  • Number of Participants With Vital Signs Abnormalities [ Time Frame: Baseline up to Day 77 ] [ Designated as safety issue: Yes ]
    Criteria for vital signs abnormalities: supine systolic blood pressure (SBP) <90 millimeter of mercury (mm Hg), supine diastolic BP (DBP) <50 mm Hg, supine pulse rate <40 beats per minute (bpm), > 120 bpm. Maximum increase or decrease from baseline in supine SBP >=30 mm Hg and maximum increase or decrease from baseline in supine DBP >=20 mm Hg.

  • Number of Participants With Electrocardiogram (ECG) Abnormalities [ Time Frame: Baseline up to Day 77 ] [ Designated as safety issue: Yes ]
    Criteria for potential clinical concern in ECG parameters: maximum PR interval of greater than or equal to (>=) 300 milliseconds (msec), maximum QRS interval >=140 msec, maximum QTCF interval (Fridericia's Correction) of 450 to <480 msec, 480 to <500 msec and >=500 msec, maximum increase of >=25 percent (%) for baseline value of >200 msec and >=50% for baseline value of less than or equal to (<=) 200 msec for PR interval, maximum increase from baseline of >=50% for QRS interval, maximum increase from baseline of >=30 msec to <60 msec and maximum increase from baseline of >60 msec in QTCF interval (Fridericia's Correction).

  • Number of Participants With Blood Glucose Abnormalities [ Time Frame: Baseline up to Day 32 ] [ Designated as safety issue: Yes ]
    Criteria for blood glucose abnormality: Blood glucose levels <0.6* LLN or >1.5* ULN.


Secondary Outcome Measures:
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose [ Time Frame: 0 hour (pre-dose) on Day 1, 4; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1; Day 2, 3 ] [ Designated as safety issue: No ]
    Participants who received PF-05231023 with C-terminal and N-terminal AUCtau were reported.

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose [ Time Frame: 0 hour (pre-dose) on Day 1, 4; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1; Day 2, 3 ] [ Designated as safety issue: No ]
    Participants who received PF-05231023 with C-terminal and N-terminal Tmax were reported.

  • Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose [ Time Frame: 0 hour (pre-dose) on Day 1, 4; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1; Day 2, 3 ] [ Designated as safety issue: No ]
    Participants who received PF 05231023 with C-terminal and N-terminal Cmax were reported.

  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 at Steady State [ Time Frame: 0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29 ] [ Designated as safety issue: No ]
    Participants who received PF-05231023 with C-terminal and N-terminal AUCtau at steady state were reported.

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05231023 at Steady State [ Time Frame: 0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) at steady state. Participants who received PF-05231023 with C-terminal and N-terminal AUClast at steady state were reported.

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 at Steady State [ Time Frame: 0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29 ] [ Designated as safety issue: No ]
    Participants who received PF-05231023 with C-terminal and N-terminal Tmax at steady state were reported.

  • Maximum Observed Plasma Concentration (Cmax) of PF-05231023 at Steady State [ Time Frame: 0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29 ] [ Designated as safety issue: No ]
    Participants who received PF 05231023 with C-terminal and N-terminal Cmax at steady state were reported.

  • Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval of PF-05231023 (Rac) [ Time Frame: 0 hour (pre-dose) on Day 1, 4, 25; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1, 25; Day 2, 3, 26, 29 ] [ Designated as safety issue: No ]
    Rac was obtained from AUCtau at steady state (Day 25) divided by AUCtau after single dose (Day 1). AUCtau was the area under the concentration-time profile from time zero to end of dosing interval, where tau = 72 hours for Day 1 and tau = 96 hours for Day 25. Participants who received PF-05231023 with C-terminal and N-terminal Rac at steady state were reported.

  • Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF- 05231023 [ Time Frame: 0 hour (pre-dose) on Day 1, 4, 25; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1, 25; Day 2, 3, 26, 29 ] [ Designated as safety issue: No ]
    Accumulation ratio based on maximum plasma concentration (Cmax) was calculated as: Rac,Cmax = Cmax at steady state (Day 25) divided by Cmax at first dose (Day 1). Participants who received PF-05231023 with C-terminal and N-terminal Rac,Cmax at steady state were reported.

  • Plasma Terminal Half-Life (t1/2) of PF-05231023 at Steady State [ Time Frame: 0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29 ] [ Designated as safety issue: No ]
    Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half at the terminal phase. Participants who received PF-05231023 with C-terminal and N-terminal t1/2 at steady state were reported.

  • Apparent Clearance (CL) of PF-05231023 at Steady State [ Time Frame: 0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29 ] [ Designated as safety issue: No ]
    Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Participants who received PF-05231023 with C-terminal and N-terminal CL at steady state were reported.

  • Volume of Distribution of PF-05231023 at Steady State (Vss) [ Time Frame: 0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29 ] [ Designated as safety issue: No ]
    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. Vss is the apparent volume of distribution at steady-state. PF-05231023 with C-terminal and N-terminal Vss at steady state were reported.

  • Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 at Steady State [ Time Frame: 0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29 ] [ Designated as safety issue: No ]
    Participants who received PF 05231023 with C-terminal and N-terminal Cmax at steady state were reported.

  • Average Plasma Concentration (Cav) of PF-05231023 at Steady State [ Time Frame: 0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29 ] [ Designated as safety issue: No ]
    Participants who received PF-05231023 with C-terminal and N-terminal Cmax at steady state were reported.


Enrollment: 50
Study Start Date: July 2011
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Drug: PF-05231023
5 mg IV twice a week for 4 weeks
Drug: PF-05231023
25 mg IV twice a week for 4 weeks
Drug: PF-05231023
100 mg IV twice a week for 4 weeks
Drug: PF-05231023
200 mg IV twice a week for 4 weeks
Placebo Comparator: Placebo Other: Placebo
0.9% w/v sodium chloride injection, United States Pharmacopeia (USP), twice a week IV for 4 weeks

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male subjects and female subjects of non-childbearing potential between the ages of 30 and 70 years, inclusive, with a historical diagnosis of type 2 diabetes mellitus, diagnosed according to the American Diabetes Association guidelines. Subjects who have other conditions but are well controlled by either diet or medications may be included as well (for example, a subject with high cholesterol level on appropriate treatment is eligible).
  • Body Mass Index (BMI) of 25 to 35.5 kg/m2, and a total body weight >50 kg (110 lbs).

Exclusion Criteria:

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
  • Diagnosis of Type 1 diabetes mellitus.
  • Evidence of diabetic complications with significant end organ damage
  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: NCT01396187

Locations
United States, California
Pfizer Investigational Site
Chula Vista, California, United States, 91911
United States, Florida
Pfizer Investigational Site
Miami, Florida, United States, 33169
Pfizer Investigational Site
South Miami, Florida, United States, 33143
United States, Kansas
Pfizer Investigational Site
Overland Park, Kansas, United States, 66212
United States, Texas
Pfizer Investigational Site
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01396187     History of Changes
Other Study ID Numbers: B2901002
Study First Received: July 6, 2011
Results First Received: December 30, 2014
Last Updated: December 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Type 2 diabetes
safety
multiple dose
intravenous

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

ClinicalTrials.gov processed this record on March 03, 2015