Diabetes Mellitus, Type 2
Conditions
Brief summary
This is a Phase 1, randomized, double-blind (sponsor open), placebo controlled study in adult Chinese participants with T2DM who are receiving metformin as background antihyperglycemic medication.
Interventions
DRUGPF-06882961
Participants will be administered active doses, taking 3 tablets twice daily (BID) for 8 weeks except Day 1 (QD)
DRUGPlacebo
3 matching placebo tablets taken twice daily (BID) except Day 1 (QD)
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Patients with T2DM who are taking metformin monotherapy as their only antihyperglycemic treatment * HbA1c greater than or equal to 7% and less than or equal to 10.5% * Total body weight \>50 kg (110 lb) with BMI of 22.5 to 45.4 kg/m\^2
Exclusion criteria
* Any condition possibly affecting drug absorption * Diagnosis of Type 1 diabetes mellitus or secondary forms of diabetes * History of myocardial infarction, unstable angina, arterial revascularization, stroke, heart failure, or transient ischemic attack within 6 months of Screening * Any malignancy not considered cured * Personal or family history of MTC or MEN2, or participants with suspected MTC * Acute pancreatitis or history of chronic pancreatitis * Acute gallbladder disease * Known history of HIV, hepatitis B, hepatitis C or syphilis, or positive testing of them * Supine blood pressure greater than or equal to 160 mmHg (systolic) or greater than or equal to 100 mmHg (diastolic) * Clinically relevant ECG abnormalities * Positive urine drug test * Clinical relevant laboratory tests abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration, Steady State (Cmax,ss) of PF-06882961 in Participants Received 40 mg BID, 80 mg BID, and 120 mg BID PF-06882961 | Pre-dose, 1, 2, 4, 6, 8, 10, 12, 14, 24 hours post dose on Day 21 (40 mg BID), 35 (80 mg BID), and 56 (120 mg BID) | Cmax,ss was measured on Day 21, 35, and 56 for dose 40 mg BID, 80 mg BID, and 120 mg BID, respectively. The planned analysis was not considered reliable by the sponsor. |
| Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC24) of PF-06882961 10 mg Single Dose on Day 1 | Pre-dose, 1, 2, 4, 6, 8, 10, 12, 14, 24 hours post dose on Day 1 | AUC24 is the area under the plasma concentration-time profile from time zero to the time 24 hours. The planned analysis was not considered reliable by the sponsor. |
| Maximum Observed Concentration (Cmax) of PF-06882961 10 mg Single Dose on Day 1 | Pre-dose, 1, 2, 4, 6, 8, 10, 12, 14, 24 hours post dose on Day 1 | Cmax is the maximum observed plasma concentration over 24 hours. The planned analysis was not considered reliable by the sponsor. |
| AUC24 of PF-06882961 in Participants Received 40 mg BID, 80 mg BID, and 120 mg BID PF-06882961 | Pre-dose, 1, 2, 4, 6, 8, 10, 12, 14, 24 hours post dose on Day 21 (40 mg BID), 35 (80 mg BID), and 56 (120 mg BID) | AUC24 was measured on Day 21, 35, and 56 for dose 40 mg BID, 80 mg BID, and 120 mg BID, respectively. The planned analysis was not considered reliable by the sponsor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Baseline up to 14 days after last dose (Day 70) | Supine blood pressure and pulse rate were measured with the participant's arm supported at the level of the heart and recorded to the nearest mmHg after approximately 5 minutes of rest and maximum absolute values and maximum changes from baseline from time-matched baseline were evaluated at the investigator's discretion. |
| Number of Participants With Abnormal Electrocardiogram (ECG) | Baseline up to 14 days after last dose (Day 70) | Standard 12-lead ECGs utilizing limb leads were collected using an ECG machine that automatically calculated the heart rate and measures PR, QT, and QT interval corrected for heart rate (QTc) and QRS complex. |
| Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Baseline up to 35 days after last dose (Day 91) | An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event was defined as any untoward medical occurrence that,at any dose:resulted in death;was life-threatening;required inpatient hospitalization or prolongation of existing hospitalization;resulted in persistent disability/incapacity; was a congenital anomaly/birth defect;or other serious situations such as important medical events. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE. |
| Number of Participants With Laboratory Abnormalities | Baseline up to 14 days after last dose (Day 70) | Laboratory tests (including hematological, clinical chemistry, urinalysis tests) were reported and abnormality was determined at the investigator's discretion. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo BID (except QD in the morning on Day 1) from Days 1-56. | 5 |
| PF-06882961 BID Participants received PF-06882961 BID (except QD in the morning on Day 1) following dose titration schema: 10 mg on Days 1-7, 20 mg on Days 8-14, 40 mg on Days 15-21, 60 mg on Days 22-28, 80 mg on Days 29-35, 100 mg BID on Days 36-42, 120 mg from Days 43-56. | 15 |
| Total | 20 |
Baseline characteristics
| Characteristic | Placebo | PF-06882961 BID | Total |
|---|---|---|---|
| Age, Continuous Mean (SD) | 50 Years STANDARD_DEVIATION 4.64 | 49.5 Years STANDARD_DEVIATION 7.22 | 49.6 Years STANDARD_DEVIATION 6.56 |
| Age, Customized 20-44 Years | 1 Participants | 4 Participants | 5 Participants |
| Age, Customized 45-60 Years | 4 Participants | 11 Participants | 15 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 15 Participants | 20 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 5 Participants | 15 Participants | 20 Participants |
| Sex: Female, Male Female | 1 Participants | 8 Participants | 9 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 15 |
| other Total, other adverse events | 5 / 5 | 14 / 15 |
| serious Total, serious adverse events | 0 / 5 | 0 / 15 |
Outcome results
Primary
Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC24) of PF-06882961 10 mg Single Dose on Day 1
AUC24 is the area under the plasma concentration-time profile from time zero to the time 24 hours. The planned analysis was not considered reliable by the sponsor.
Time frame: Pre-dose, 1, 2, 4, 6, 8, 10, 12, 14, 24 hours post dose on Day 1
Population: All participants randomized and treated with PF-06882961 who had at least 1 plasma concentration value collected.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06882961 10 mg Single Dose | Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC24) of PF-06882961 10 mg Single Dose on Day 1 | 287.4 nanogram*hour per milliter (ng*hr/mL) | Geometric Coefficient of Variation 52 |
Primary
AUC24 of PF-06882961 in Participants Received 40 mg BID, 80 mg BID, and 120 mg BID PF-06882961
AUC24 was measured on Day 21, 35, and 56 for dose 40 mg BID, 80 mg BID, and 120 mg BID, respectively. The planned analysis was not considered reliable by the sponsor.
Time frame: Pre-dose, 1, 2, 4, 6, 8, 10, 12, 14, 24 hours post dose on Day 21 (40 mg BID), 35 (80 mg BID), and 56 (120 mg BID)
Population: All participants randomized and treated with PF-06882961 who had at least 1 plasma concentration value collected.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06882961 10 mg Single Dose | AUC24 of PF-06882961 in Participants Received 40 mg BID, 80 mg BID, and 120 mg BID PF-06882961 | 1446 ng*hr/mL | Geometric Coefficient of Variation 236 |
| PF-06882961 BID | AUC24 of PF-06882961 in Participants Received 40 mg BID, 80 mg BID, and 120 mg BID PF-06882961 | 1012 ng*hr/mL | Geometric Coefficient of Variation 1414 |
| PF-06882961 120 mg BID | AUC24 of PF-06882961 in Participants Received 40 mg BID, 80 mg BID, and 120 mg BID PF-06882961 | 984.9 ng*hr/mL | Geometric Coefficient of Variation 2327 |
Primary
Maximum Observed Concentration (Cmax) of PF-06882961 10 mg Single Dose on Day 1
Cmax is the maximum observed plasma concentration over 24 hours. The planned analysis was not considered reliable by the sponsor.
Time frame: Pre-dose, 1, 2, 4, 6, 8, 10, 12, 14, 24 hours post dose on Day 1
Population: All participants randomized and treated with PF-06882961 who had at least 1 plasma concentration value collected.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06882961 10 mg Single Dose | Maximum Observed Concentration (Cmax) of PF-06882961 10 mg Single Dose on Day 1 | 37.37 nanogram per milliter (ng/mL) | Geometric Coefficient of Variation 39 |
Primary
Maximum Observed Concentration, Steady State (Cmax,ss) of PF-06882961 in Participants Received 40 mg BID, 80 mg BID, and 120 mg BID PF-06882961
Cmax,ss was measured on Day 21, 35, and 56 for dose 40 mg BID, 80 mg BID, and 120 mg BID, respectively. The planned analysis was not considered reliable by the sponsor.
Time frame: Pre-dose, 1, 2, 4, 6, 8, 10, 12, 14, 24 hours post dose on Day 21 (40 mg BID), 35 (80 mg BID), and 56 (120 mg BID)
Population: All participants randomized and treated with PF-06882961 who had at least 1 plasma concentration value collected.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06882961 10 mg Single Dose | Maximum Observed Concentration, Steady State (Cmax,ss) of PF-06882961 in Participants Received 40 mg BID, 80 mg BID, and 120 mg BID PF-06882961 | 150.3 ng/mL | Geometric Coefficient of Variation 176 |
| PF-06882961 BID | Maximum Observed Concentration, Steady State (Cmax,ss) of PF-06882961 in Participants Received 40 mg BID, 80 mg BID, and 120 mg BID PF-06882961 | 98.92 ng/mL | Geometric Coefficient of Variation 1059 |
| PF-06882961 120 mg BID | Maximum Observed Concentration, Steady State (Cmax,ss) of PF-06882961 in Participants Received 40 mg BID, 80 mg BID, and 120 mg BID PF-06882961 | 110.5 ng/mL | Geometric Coefficient of Variation 3069 |
Secondary
Number of Participants With Abnormal Electrocardiogram (ECG)
Standard 12-lead ECGs utilizing limb leads were collected using an ECG machine that automatically calculated the heart rate and measures PR, QT, and QT interval corrected for heart rate (QTc) and QRS complex.
Time frame: Baseline up to 14 days after last dose (Day 70)
Population: All participants randomly assigned to study intervention and who had at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06882961 10 mg Single Dose | Number of Participants With Abnormal Electrocardiogram (ECG) | PR interval not otherwise specified (msec) %change >=50% | 0 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF not otherwise specified (msec) 450 < Value <=480 | 1 Participants |
| PF-06882961 BID | Number of Participants With Abnormal Electrocardiogram (ECG) | PR interval not otherwise specified (msec) %change >=50% | 1 Participants |
| PF-06882961 BID | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF not otherwise specified (msec) 450 < Value <=480 | 1 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Supine blood pressure and pulse rate were measured with the participant's arm supported at the level of the heart and recorded to the nearest mmHg after approximately 5 minutes of rest and maximum absolute values and maximum changes from baseline from time-matched baseline were evaluated at the investigator's discretion.
Time frame: Baseline up to 14 days after last dose (Day 70)
Population: All participants randomly assigned to study intervention and who had at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06882961 10 mg Single Dose | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine systolic blood pressure (mmHg) change >=30 mm Hg increase | 1 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine diastolic blood pressure (mmHg) change >=20 mm Hg decrease | 0 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine diastolic blood pressure (mmHg) change >=20 mm Hg increase | 1 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine pulse rate (beats per minute [bpm]) value >120 bpm | 0 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine systolic blood pressure (mmHg) change >=30 mm Hg decrease | 0 Participants |
| PF-06882961 BID | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine pulse rate (beats per minute [bpm]) value >120 bpm | 1 Participants |
| PF-06882961 BID | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine systolic blood pressure (mmHg) change >=30 mm Hg increase | 3 Participants |
| PF-06882961 BID | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine systolic blood pressure (mmHg) change >=30 mm Hg decrease | 2 Participants |
| PF-06882961 BID | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine diastolic blood pressure (mmHg) change >=20 mm Hg increase | 6 Participants |
| PF-06882961 BID | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine diastolic blood pressure (mmHg) change >=20 mm Hg decrease | 1 Participants |
Secondary
Number of Participants With Laboratory Abnormalities
Laboratory tests (including hematological, clinical chemistry, urinalysis tests) were reported and abnormality was determined at the investigator's discretion.
Time frame: Baseline up to 14 days after last dose (Day 70)
Population: All participants randomly assigned to study intervention and who had at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Chemistry - high-density lipoprotein cholesterol (mg/dL) <0.8xlower limit of normal (LLN) | 2 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Glucose ≥1 | 3 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Hematology - Neutrophils (10^3/mm3) >1.2xupper limit of norma (ULN) | 0 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Ketones (Scalar) ≥1 | 0 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Chemistry - Triglycerides (mg/dL) >1.3xULN | 0 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Chemistry - Urate (mg/dL) >1.2xULN | 0 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Hemoglobin (Scalar) ≥1 | 1 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Chemistry - Thyrotropin (uIU/mL) <0.8xLLN | 0 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Urobilinogen ≥1 | 0 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Hematology - Basophils (10^3/mm3) >1.2xULN | 0 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Nitrite (Scalar) ≥1 | 0 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Chemistry - Bile Acid (umol/L) >1.0xULN | 0 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Leukocyte Esterase (Scalar) ≥1 | 0 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Protein ≥1 | 0 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Leukocyte Esterase (Scalar) ≥1 | 2 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Hematology - Neutrophils (10^3/mm3) >1.2xupper limit of norma (ULN) | 1 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Hematology - Basophils (10^3/mm3) >1.2xULN | 1 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Chemistry - Urate (mg/dL) >1.2xULN | 4 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Chemistry - high-density lipoprotein cholesterol (mg/dL) <0.8xlower limit of normal (LLN) | 1 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Chemistry - Triglycerides (mg/dL) >1.3xULN | 3 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Chemistry - Thyrotropin (uIU/mL) <0.8xLLN | 1 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Chemistry - Bile Acid (umol/L) >1.0xULN | 1 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Glucose ≥1 | 6 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Ketones (Scalar) ≥1 | 2 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Protein ≥1 | 1 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Hemoglobin (Scalar) ≥1 | 3 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Urobilinogen ≥1 | 2 Participants |
| PF-06882961 BID | Number of Participants With Laboratory Abnormalities | Urinalysis - Urine Nitrite (Scalar) ≥1 | 1 Participants |
Secondary
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event was defined as any untoward medical occurrence that,at any dose:resulted in death;was life-threatening;required inpatient hospitalization or prolongation of existing hospitalization;resulted in persistent disability/incapacity; was a congenital anomaly/birth defect;or other serious situations such as important medical events. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE.
Time frame: Baseline up to 35 days after last dose (Day 91)
Population: All participants randomly assigned to study intervention and who had at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06882961 10 mg Single Dose | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Participants with non-serious AEs | 5 Participants |
| PF-06882961 10 mg Single Dose | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Participants with serious adverse events | 0 Participants |
| PF-06882961 BID | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Participants with non-serious AEs | 14 Participants |
| PF-06882961 BID | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Participants with serious adverse events | 0 Participants |