Type 2 Diabetes Mellitus (T2DM)
Conditions
Keywords
T2DM, obesity, safety, multiple dose, intravenous
Brief summary
This is a trial in obese subjects to study the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple doses of PF-05231023.
Interventions
OTHERPlacebo
0.9% w/v sodium chloride injection, United States Pharmacopeia (USP), twice a week for 4 weeks.
100 mg IV infusion twice a week for 4 weeks
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects of non-childbearing potential between the ages of 21 and 70. * Subjects with a BMI of 30 to 45.4 kg/m2 and total body weight \>110 lbs.
Exclusion criteria
* Recent (6 months) unstable concurrent disease. * History of allergic disease or drug allergies. * Any condition affecting food consumption or absorption.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Day -7 through the last follow-up (Day 68) | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were also reported for the 7-day pre-randomization period. |
| Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Days -7 up to the last follow-up (Day 68) | Vital signs included supine systolic blood pressure, diastolic blood pressure and pulse rate. Vital signs criteria of potential clinical concern were 1), blood pressure: systolic greater than or equal to (\>=)30 millimeters of mercury (mm Hg) change from baseline in the same posture or systolic less than (\<)90 mm Hg; diastolic \>=20 mm Hg change from baseline in the same posture or diastolic \<50 mm Hg; 2), Pulse rate: supine/Sitting: \<40 or greater than (\>) 120 beats per minute (bpm); Standing: \<40 or \>140 bpm. |
| Number of Participants With Electrocardiogram (ECG) Data Met Criteria of Potential Clinical Concern | Days -7 up to the last follow-up (Day 68) | ECG criteria of potential clinical concern were 1), PR interval:\>=300 msec, \>=25% increase when baseline \>200 msec, or \>=50% increase when baseline \<=200 msec; 2), QRS interval:\>=140 msec, or \>=50% increase from baseline; 3), QT interval corrected for heart rate (QTc)/QTc interval using Fridericia's formula (QTcF):\>=500 msec, QTcF interval: absolute value \>=450 - \<480 msec(borderline), \>=480 msec (prolonged), absolute change 30 - \<60 msec (borderline) or \>=60 msec (prolonged). 12-lead ECG (triplicate) was performed on Day 0 and 12-lead ECG (singlet) was performed at other times. |
| Number of Participants With Positive Anti-PF-05231023 Antibodies and Neutralizing Antibodies. | Days 1 up to the last follow-up (Day 68) | Anti-PF-05231023 antibodies were analyzed using a tiered testing strategy of screen, confirm, and titer characterization. Positive was defined as titer value \>=6.23 and negative was defined as titer value \<6.23. Samples tested positive were also to be analyzed in a neutralization assay to determine whether or not they were neutralizing or non-neutralizing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Concentration at Steady State (Cav) of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) | Day 25 | — |
| Time for Cmax (Tmax)of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) | Day 25 | — |
| Number of Participants With Abnormal Clinical Laboratory Measurements | Days -7 up to the last follow-up (Day 68) | The total number of participants with laboratory test abnormalities without regard to baseline abnormality was assessed. |
| Terminal Elimination Half-life (t1/2)of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) | Day 25 | — |
| Observed Accumulation Ratio (Rac) for Cmax and AUCtau of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) | Day 25 | — |
| Clearance (CL)of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) | Day 25 | — |
| Area Under the Concentration Versus Time Curve From Time 0 to Tau, the Dosing Interval (AUCtau) of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) | Days 1 and 25 | — |
| Maximum Plasma Concentration (Cmax) of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) | Days 1 and 25 | — |
| Lowest Concentration Observed During Dosing Interval (Cmin) of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) | Day 25 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (normal saline) was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25. | 2 |
| PF-05231023 100 mg PF-05231023 100 mg was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25. | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | PF-05231023 100 mg | Total |
|---|---|---|---|
| Age, Continuous | 39.0 years STANDARD_DEVIATION 4.2 | 34.0 years STANDARD_DEVIATION 5.7 | 36.5 years STANDARD_DEVIATION 5 |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were also reported for the 7-day pre-randomization period.
Time frame: Day -7 through the last follow-up (Day 68)
Population: All participants who received at least 1 dose of study medication (PF-05231023 or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) | 2 Participants |
| PF-05231023 100 mg | Number of Participants With Adverse Events (AEs) | 2 Participants |
Primary
Number of Participants With Electrocardiogram (ECG) Data Met Criteria of Potential Clinical Concern
ECG criteria of potential clinical concern were 1), PR interval:\>=300 msec, \>=25% increase when baseline \>200 msec, or \>=50% increase when baseline \<=200 msec; 2), QRS interval:\>=140 msec, or \>=50% increase from baseline; 3), QT interval corrected for heart rate (QTc)/QTc interval using Fridericia's formula (QTcF):\>=500 msec, QTcF interval: absolute value \>=450 - \<480 msec(borderline), \>=480 msec (prolonged), absolute change 30 - \<60 msec (borderline) or \>=60 msec (prolonged). 12-lead ECG (triplicate) was performed on Day 0 and 12-lead ECG (singlet) was performed at other times.
Time frame: Days -7 up to the last follow-up (Day 68)
Population: All participants who received at least 1 dose of study medication (PF-05231023 or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Met Criteria of Potential Clinical Concern | 1 Participants |
| PF-05231023 100 mg | Number of Participants With Electrocardiogram (ECG) Data Met Criteria of Potential Clinical Concern | 0 Participants |
Primary
Number of Participants With Positive Anti-PF-05231023 Antibodies and Neutralizing Antibodies.
Anti-PF-05231023 antibodies were analyzed using a tiered testing strategy of screen, confirm, and titer characterization. Positive was defined as titer value \>=6.23 and negative was defined as titer value \<6.23. Samples tested positive were also to be analyzed in a neutralization assay to determine whether or not they were neutralizing or non-neutralizing.
Time frame: Days 1 up to the last follow-up (Day 68)
Population: All participants who received at least 1 dose of active study medication (PF-05231023). Neutralizing antibodies were not tested because all participants who received PF-05231023 100 mg tested negative for anti-PF-05231023 antibodies.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Positive Anti-PF-05231023 Antibodies and Neutralizing Antibodies. | 0 Participants |
| PF-05231023 100 mg | Number of Participants With Positive Anti-PF-05231023 Antibodies and Neutralizing Antibodies. | 0 Participants |
Primary
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern
Vital signs included supine systolic blood pressure, diastolic blood pressure and pulse rate. Vital signs criteria of potential clinical concern were 1), blood pressure: systolic greater than or equal to (\>=)30 millimeters of mercury (mm Hg) change from baseline in the same posture or systolic less than (\<)90 mm Hg; diastolic \>=20 mm Hg change from baseline in the same posture or diastolic \<50 mm Hg; 2), Pulse rate: supine/Sitting: \<40 or greater than (\>) 120 beats per minute (bpm); Standing: \<40 or \>140 bpm.
Time frame: Days -7 up to the last follow-up (Day 68)
Population: All participants who received at least 1 dose of study medication (PF-05231023 or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | 0 Participants |
| PF-05231023 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | 0 Participants |
Secondary
Area Under the Concentration Versus Time Curve From Time 0 to Tau, the Dosing Interval (AUCtau) of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold)
Time frame: Days 1 and 25
Population: AUCtau for C-terminus and N-terminus of PF-05231023 and CVX-2000 were not summarized due to the premature termination of the study.
Secondary
Average Concentration at Steady State (Cav) of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold)
Time frame: Day 25
Population: Cav for C-terminus and N-terminus of PF-05231023 and CVX-2000 were not reported due to the premature termination of the study.
Secondary
Clearance (CL)of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold)
Time frame: Day 25
Population: CL for C-terminus and N-terminus of PF-05231023 and CVX-2000 were not summarzied due to the premature termination of the study.
Secondary
Lowest Concentration Observed During Dosing Interval (Cmin) of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold)
Time frame: Day 25
Population: Cmin for C-terminus and N-terminus of PF-05231023 and CVX-2000 were not summarized due to the premature termination of the study.
Secondary
Maximum Plasma Concentration (Cmax) of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold)
Time frame: Days 1 and 25
Population: Cmax for C-terminus and N-terminus of PF-05231023 and CVX-2000 were not summarized due to the premature termination of the study.
Secondary
Number of Participants With Abnormal Clinical Laboratory Measurements
The total number of participants with laboratory test abnormalities without regard to baseline abnormality was assessed.
Time frame: Days -7 up to the last follow-up (Day 68)
Population: All participants who received at least 1 dose of study medication (PF-05231023 or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Abnormal Clinical Laboratory Measurements | 0 Participants |
| PF-05231023 100 mg | Number of Participants With Abnormal Clinical Laboratory Measurements | 0 Participants |
Secondary
Observed Accumulation Ratio (Rac) for Cmax and AUCtau of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold)
Time frame: Day 25
Population: Rac for C-terminus and N-terminus of PF-05231023 and CVX-2000 were not summarzied due to the premature termination of the study.
Secondary
Terminal Elimination Half-life (t1/2)of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold)
Time frame: Day 25
Population: t1/2 for C-terminus and N-terminus of PF-05231023 and CVX-2000 were not summarzied due to the premature termination of the study.
Secondary
Time for Cmax (Tmax)of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold)
Time frame: Day 25
Population: Tmax for C-terminus and N-terminus of PF-05231023 and CVX-2000 were not summarzied due to the premature termination of the study.