Back to resultsSafety and Tolerability of Ascending Intravenous Doses of PF-05231023 In Adult Subjects With Type 2 Diabetes
Primary Purpose
Diabetes Mellitus, Type 2
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PF-05231023
PF-05231023
PF-05231023
PF-05231023
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring Type 2 diabetes, safety, multiple dose, intravenous
Eligibility 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
Sites / Locations
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Treatment
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants With Abnormal Physical Examination Findings
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)
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
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
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
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
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
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
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
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
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
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
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
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)
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
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
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
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)
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
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
Participants who received PF-05231023 with C-terminal and N-terminal Cmax at steady state were reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01396187
Brief Title
Safety and Tolerability of Ascending Intravenous Doses of PF-05231023 In Adult Subjects With Type 2 Diabetes
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
May 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
Type 2 diabetes, safety, multiple dose, intravenous
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
PF-05231023
Intervention Description
5 mg IV twice a week for 4 weeks
Intervention Type
Drug
Intervention Name(s)
PF-05231023
Intervention Description
25 mg IV twice a week for 4 weeks
Intervention Type
Drug
Intervention Name(s)
PF-05231023
Intervention Description
100 mg IV twice a week for 4 weeks
Intervention Type
Drug
Intervention Name(s)
PF-05231023
Intervention Description
200 mg IV twice a week for 4 weeks
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
0.9% w/v sodium chloride injection, United States Pharmacopeia (USP), twice a week IV for 4 weeks
Primary Outcome Measure Information:
Title
Number of Participants With Abnormal Physical Examination Findings
Description
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.
Time Frame
Baseline up to Day 42
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description
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.
Time Frame
Baseline up to Day 77
Title
Number of Participants With Abnormal Laboratory Values
Description
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.
Time Frame
Baseline up to Day 42
Title
Number of Participants With Vital Signs Abnormalities
Description
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.
Time Frame
Baseline up to Day 77
Title
Number of Participants With Electrocardiogram (ECG) Abnormalities
Description
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).
Time Frame
Baseline up to Day 77
Title
Number of Participants With Blood Glucose Abnormalities
Description
Criteria for blood glucose abnormality: Blood glucose levels <0.6* LLN or >1.5* ULN.
Time Frame
Baseline up to Day 32
Secondary Outcome Measure Information:
Title
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose
Description
Participants who received PF-05231023 with C-terminal and N-terminal AUCtau were reported.
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
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose
Description
Participants who received PF-05231023 with C-terminal and N-terminal Tmax were reported.
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
Title
Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose
Description
Participants who received PF 05231023 with C-terminal and N-terminal Cmax were reported.
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
Title
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 at Steady State
Description
Participants who received PF-05231023 with C-terminal and N-terminal AUCtau at steady state were reported.
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
Title
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05231023 at Steady State
Description
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 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
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 at Steady State
Description
Participants who received PF-05231023 with C-terminal and N-terminal Tmax at steady state were reported.
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
Title
Maximum Observed Plasma Concentration (Cmax) of PF-05231023 at Steady State
Description
Participants who received PF 05231023 with C-terminal and N-terminal Cmax at steady state were reported.
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
Title
Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval of PF-05231023 (Rac)
Description
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.
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
Title
Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF- 05231023
Description
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.
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
Title
Plasma Terminal Half-Life (t1/2) of PF-05231023 at Steady State
Description
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.
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
Title
Apparent Clearance (CL) of PF-05231023 at Steady State
Description
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.
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
Title
Volume of Distribution of PF-05231023 at Steady State (Vss)
Description
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.
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
Title
Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 at Steady State
Description
Participants who received PF 05231023 with C-terminal and N-terminal Cmax at steady state were reported.
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
Title
Average Plasma Concentration (Cav) of PF-05231023 at Steady State
Description
Participants who received PF-05231023 with C-terminal and N-terminal Cmax at steady state were reported.
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States
Facility Name
Pfizer Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33169
Country
United States
Facility Name
Pfizer Investigational Site
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Pfizer Investigational Site
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66212
Country
United States
Facility Name
Pfizer Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B2901002&StudyName=Safety%20and%20Tolerability%20of%20Ascending%20Intravenous%20Doses%20of%20PF-05231023%20In%20Adult%20Subjects%20with%20Type%202%20Diabetes
Description
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Safety and Tolerability of Ascending Intravenous Doses of PF-05231023 In Adult Subjects With Type 2 Diabetes
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