Safety And Tolerability Of Escalating Intravenous Doses Of PF-05231023 In Adult Subjects With Type 2 Diabetes

NCT01285518 | Completed Phase 1 Results

• 1 other identifier: B2901001
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Diabetes Mellitus, Type 2

Keywords

Type 2 diabetes; intravenous; single dose

Outcome Measures

Primary Outcomes (25)

• Number of Participants With Abnormal Physical Examination Findings

  Physical examination included assessment of height, weight, blood pressure and pulse rate. Criteria for abnormal physical findings was based on investigator's discretion and were reported as adverse event (AE), as planned.

  Day -1 up to Day 22

• Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

  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 22 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

  Day 1 up to Day 22

• Number of Participants With Abnormal Laboratory Values

  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/\>1.75\*ULN); neutrophils, lymphocytes (\<0.8\*LLN/\>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/\>1.2\*ULN); creatinine, urea (\>1.3\*ULN); glucose (\<0.6\*LLN/\>1.5\*ULN); uric acid (\>1.2\*ULN); sodium, potassium, chloride, calcium, bicarbonate (\<0.9\*LLN/\>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 was reported.

  Day -1 up to Day 15

• Number of Participants With Vital Signs Abnormalities

  Criteria for vital signs abnormalities: supine systolic blood pressure (SBP) \<90 millimeter of mercury (mmHg), supine diastolic BP (DBP) \<50 mmHg, supine pulse rate \<40 beats per minute (bpm). Maximum increase or decrease from baseline in supine SBP \>=30 mmHg and maximum increase or decrease from baseline in supine DBP \>=20 mmHg.

  Day 1 up to Day 15

• Number of Participants With Electrocardiogram (ECG) Abnormalities

  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 for PR interval and maximum increase of \>=50% for baseline value of less than or equal to (\<=) 200 msec 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).

  Screening up to Day 15

• Number of Participants With Hypoglycemic Adverse Event Based on Capillary Glucose Levels

  Capillary blood glucose levels were collected to observe any hypoglycemic adverse events. Hypoglycemia was assessed as following categories; Severe hypoglycemia (1. Participant was unable to treat himself/herself, requiring assistance of another person to actively administer carbohydrate, glucagon 2. Exhibited one of following neurological symptoms memory loss, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure or loss of consciousness, 3. Glucose \<50 mg/dL confirmed on repeat measure); Documented symptomatic hypoglycemia (1. Symptoms of hypoglycaemia accompanied by a measured glucose concentration \<=70 mg/dL); asymptomatic hypoglycemia (not accompanied by typical symptoms of hypoglycaemia but with a measured glucose concentration \<=70 mg/dL), and probable hypoglycemia (typical symptoms of hypoglycaemia are not accompanied by a glucose determination, but was presumably caused by a plasma glucose concentration \<=70 mg/dL).

  Day 0 up to Day 22

• Number of Participants With Blood Glucose Abnormalities

  Criteria for blood glucose abnormality: Blood glucose levels \<0.6\*lower limit of normal (LLN) or \>1.5\*upper limit of normal (ULN).

  Day -1 up to Day 15

• Number of Participants With Anti-Drug Antibodies (ADA): Day 1

  Assays for the determination of human anti-drug (Anti-PF-05231023) antibodies (ADA) was performed.

  Day 1

• Number of Participants With Anti-Drug Antibodies (ADA): Day 8

  Assays for the determination of human anti-drug (Anti-PF-05231023) antibodies (ADA) was performed.

  Day 8

• Number of Participants With Anti-Drug Antibodies (ADA): Day 15

  Assays for the determination of human anti-drug (Anti-PF-05231023) antibodies (ADA) was performed.

  Day 15

• Number of Participants With Anti-Drug Antibodies (ADA): Day 22

  Assays for the determination of human anti-drug (Anti-PF-05231023) antibodies (ADA) was performed.

  Day 22

• Number of Participants With Anti-Drug Antibodies (ADA): Day 34

  Assays for the determination of human anti-drug (Anti-PF-05231023) antibodies (ADA) was performed.

  Day 34

• Insulin-like Growth Factor - 1 (IGF-1), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-2 (IGFBP-2), Growth Hormone (GH) Levels: Day 1

  Plasma samples for IGF-1, and GH were analyzed using a validated, sensitive, and specific immunochromatographic membrane assay (ICMA) fluorescence method. Plasma samples for IGFBP-1, IGFBP-2 were assayed using a validated, sensitive, and specific colorimetric sandwich (enzyme-linked immunosorbent assay) ELISA method.

  Day 1

• Insulin-like Growth Factor - 1 (IGF-1), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-2 (IGFBP-2), Growth Hormone (GH) Levels: Day 2

  Plasma samples for IGF-1, and GH were analyzed using a validated, sensitive, and specific immunochromatographic membrane assay (ICMA) fluorescence method. Plasma samples for IGFBP-1, IGFBP-2 were assayed using a validated, sensitive, and specific colorimetric sandwich ELISA method.

  Day 2

• Insulin-like Growth Factor - 1 (IGF-1), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-2 (IGFBP-2), Growth Hormone (GH) Levels: Day 3

  Plasma samples for IGF-1, and GH were analyzed using a validated, sensitive, and specific immunochromatographic membrane assay (ICMA) fluorescence method. Plasma samples for IGFBP-1, IGFBP-2 were assayed using a validated, sensitive, and specific colorimetric sandwich ELISA method.

  Day 3

• Insulin-like Growth Factor - 1 (IGF-1), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-2 (IGFBP-2), Growth Hormone (GH) Levels: Day 5

  Plasma samples for IGF-1, and GH were analyzed using a validated, sensitive, and specific immunochromatographic membrane assay (ICMA) fluorescence method. Plasma samples for IGFBP-1, IGFBP-2 were assayed using a validated, sensitive, and specific colorimetric sandwich ELISA method.

  Day 5

• Insulin-like Growth Factor - 1 (IGF-1), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-2 (IGFBP-2), Growth Hormone (GH) Levels: Day 7

  Plasma samples for IGF-1, and GH were analyzed using a validated, sensitive, and specific immunochromatographic membrane assay (ICMA) fluorescence method. Plasma samples for IGFBP-1, IGFBP-2 were assayed using a validated, sensitive, and specific colorimetric sandwich ELISA method.

  Day 7

• Insulin-like Growth Factor - 1 (IGF-1), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-2 (IGFBP-2), Growth Hormone (GH) Levels: Day 15

  Plasma samples for IGF-1, and GH were analyzed using a validated, sensitive, and specific immunochromatographic membrane assay (ICMA) fluorescence method. Plasma samples for IGFBP-1, IGFBP-2 were assayed using a validated, sensitive, and specific colorimetric sandwich ELISA method.

  Day 15

• Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels: Day 1

  Plasma samples were assayed using a validated, sensitive, and specific ICMA fluorescence method.

  Day 1

• Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels: Day 2

  Plasma samples were assayed using a validated, sensitive, and specific ICMA fluorescence method.

  Day 2

• Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels: Day 3

  Plasma samples were assayed using a validated, sensitive, and specific ICMA fluorescence method.

  Day 3

• Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels: Day 5

  Plasma samples were assayed using a validated, sensitive, and specific ICMA fluorescence method.

  Day 5

• Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels: Day 7

  Plasma samples were assayed using a validated, sensitive, and specific ICMA fluorescence method.

  Day 7

• Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels: Day 15

  Plasma samples were assayed using a validated, sensitive, and specific ICMA fluorescence method.

  Day 15

• Number of Participants With Abnormal Cardiac Rhythms Recorded by Telemetry

  Criteria for abnormal cardiac rhythms was based on investigator's discretion and were reported as adverse event (AE), as planned.

  From 2 hours (H) pre-dose for intravenous bolus or 2 H prior to the start of infusion on Day 1 up to 8 H post-dose for bolus or 8 H following the end of the infusion on Day 1

Secondary Outcomes (9)

• Area Under the Curve From Time Zero to Time of Last Quantifiable Plasma Concentration (AUClast) of PF-05231023

  Hour(H)-1(prior to start of infusion[In] or 1 H pre-dose to bolus[Bo]),H-0.5(0.5 H post start of In or 0.5 H pre-dose to Bo),H 0(end of In or prior to Bo),0.25,0.5,1,1.5,2,3,5,8,12 H post end of In or post-dose to Bo on Day 1;Day 2,3,4,5,6,8,15,22

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023

  Hour(H)-1(prior to start of infusion[In] or 1 H pre-dose to bolus[Bo]),H-0.5(0.5 H post start of In or 0.5 H pre-dose to Bo),H 0(end of In or prior to Bo),0.25,0.5,1,1.5,2,3,5,8,12 H post end of In or post-dose to Bo on Day 1;Day 2,3,4,5,6,8,15,22

• Maximum Observed Plasma Concentration (Cmax) of PF-05231023

  Hour(H)-1(prior to start of infusion[In] or 1 H pre-dose to bolus[Bo]),H-0.5(0.5 H post start of In or 0.5 H pre-dose to Bo),H 0(end of In or prior to Bo),0.25,0.5,1,1.5,2,3,5,8,12 H post end of In or post-dose to Bo on Day 1;Day 2,3,4,5,6,8,15,22

• Plasma Terminal Half-Life (t1/2) of PF-05231023

  Hour(H)-1(prior to start of infusion[In] or 1 H pre-dose to bolus[Bo]),H-0.5(0.5 H post start of In or 0.5 H pre-dose to Bo),H 0(end of In or prior to Bo),0.25,0.5,1,1.5,2,3,5,8,12 H post end of In or post-dose to Bo on Day 1;Day 2,3,4,5,6,8,15,22

• Apparent Clearance (CL) of PF-05231023 for Intravenous Bolus Dosing

  Hour (H)-1 (1 H pre-dose to bolus [Bo]),H-0.5(0.5 H pre-dose to Bo),H 0 (prior to Bo),0.25,0.5,1,1.5,2,3,5,8,12 H post-dose to Bo on Day 1;Day 2,3,4,5,6,8,15,22

Study Arms (2)

Treatment

EXPERIMENTAL

Drug: PF-05231023

Placebo

PLACEBO COMPARATOR

0.9% w/v sodium chloride injection, USP

Other: Placebo

Interventions

PF-05231023 DRUG

0.5 mg QD IV x 1 day

Treatment

Placebo OTHER

0.9% w/v sodium chloride injection, USP QD IVx 1 day

Placebo

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects between the ages of 30 and 65 years, inclusive, with a historical diagnosis of type 2 diabetes mellitus, diagnosed according to the American Diabetes Association guidelines.
• Body Mass Index (BMI) of 25 to 35.5 kg/m2, and a total body weight \>50 kg (110 lbs).
• HbA1c \>7% and not to exceed 10.5%.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (5)

Profil Institute for Clinical Research, Inc.

Chula Vista, California, 91911, United States

Location

Comprehensive Phase One (A Division of Comprehensive NeuroScience, Inc.)

Fort Meyers, Florida, 33901, United States

Location

Elite Research Institute

Miami, Florida, 33169, United States

Location

Comprehensive Phase One (A Division of Comprehensive NeuroScience, Inc.)

Miramar, Florida, 33025, United States

Location

Cetero Research

San Antonio, Texas, 78229, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

PF-05231023

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Limitations and Caveats

Results for C0 and Vss was included as secondary endpoints as per change in the planned analysis.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2011
• First Posted: January 28, 2011
• Study Start: February 1, 2011
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: November 18, 2016
• Results First Posted: November 18, 2016

Record last verified: 2016-09

Locations

US (5)