Trial Outcomes & Findings for Study Of Two Dosing Regimens Of PF-04937319 Compared To An Approved Agent (Sitagliptin) In Patients With Type 2 Diabetes (NCT NCT01933672)
NCT ID: NCT01933672
Last Updated: 2016-09-27
Results Overview
Plasma glucose concentration was determined predose (Hour 0) and at 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16, 20, and 24 hours postdose on Days 0 (baseline) and 14. WMDG was calculated as the area under the curve (AUC) of the 12-point plasma glucose concentration-time profile divided by 24 hours.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
33 participants
Primary outcome timeframe
Prior to morning dose (Hour 0) and at 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16, 20, and 24 hours post morning dose on Days 0 (baseline) and Day 14
Results posted on
2016-09-27
Participant Flow
A total of 90 participants with type 2 diabetes mellitus (T2DM) consented for this study; of these, 47 participants were ineligible at screening visit, 43 (47.8%) transitioned into run-in phase where participants were standardized on Sponsor-provided metformin.
A total of 33 (33/90; 36.7%) participants completed metformin run-in period and were randomized and received to at least one regimen (PF-04937319 split-dose, PF-04937319 once daily, or sitagliptin).
Participant milestones
| Measure |
Metformin Run-in
Sponsor-provided, open-label metformin was administered from the run-in visit to the follow-up visit, inclusive, and it was provided as 500 milligram (mg) immediate-release tablets.
|
PF-04937319 150+100mg Then PF-04937319 300mg Then Sitagliptin
Participants received the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day and the second dose (PF-04937319 100mg) was taken with the lunch meal 5±1 hours after the morning dose, each day, for 14±2 days in the first intervention period; and then received the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the second intervention period; and then received the morning dose of sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the third intervention period.
|
PF-04937319 150+100mg Then Sitagliptin Then PF-04937319 300mg
Participants received the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day and the second dose (PF-04937319 100mg) was taken with the lunch meal 5±1 hours after the morning dose, each day, for 14±2 days in the first intervention period; and then received the morning dose of sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the second intervention period; and then received the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the third intervention period.
|
PF-04937319 300mg Then PF-04937319 150+100mg Then Sitagliptin
Participants received the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the first intervention period; and then received the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day and the second dose (PF-04937319 100mg) was taken with the lunch meal 5±1 hours after the morning dose, each day, for 14±2 days in the second intervention period; and then received the morning dose of sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days.
|
PF-04937319 300mg Then Sitagliptin Then PF-04937319 150+100mg
Participants received the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the first intervention period; and then received the morning dose of sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the second intervention period; and then received the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day and the second dose (PF-04937319 100mg) was taken with the lunch meal 5±1 hours after the morning dose, each day, for 14±2 days in the first intervention period.
|
Sitagliptin Then PF-04937319 150+100mg Then PF-04937319 300mg
Participants received the morning dose of sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the first intervention period; and then received the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day and the second dose (PF-04937319 100mg) was taken with the lunch meal 5±1 hours after the morning dose, each day, for 14±2 days in the second intervention period; and then received the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the third intervention period.
|
Sitagliptin Then PF-04937319 300mg Then PF-04937319 150+100mg
Participants received the morning dose of sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the first intervention period; and then received the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the second intervention period; and then received the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day and the second dose (PF-04937319 100mg) was taken with the lunch meal 5±1 hours after the morning dose, each day, for 14±2 days in the third intervention period.
|
|---|---|---|---|---|---|---|---|
|
Metformin Run-in Period
STARTED
|
43
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Metformin Run-in Period
Received Treatment
|
43
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Metformin Run-in Period
COMPLETED
|
33
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Metformin Run-in Period
NOT COMPLETED
|
10
|
0
|
0
|
0
|
0
|
0
|
0
|
|
First Intervention Period (12-16 Days)
STARTED
|
0
|
7
|
3
|
5
|
7
|
5
|
6
|
|
First Intervention Period (12-16 Days)
COMPLETED
|
0
|
7
|
2
|
5
|
6
|
4
|
6
|
|
First Intervention Period (12-16 Days)
NOT COMPLETED
|
0
|
0
|
1
|
0
|
1
|
1
|
0
|
|
First Washout Period (7-14 Days)
STARTED
|
0
|
7
|
2
|
5
|
6
|
4
|
6
|
|
First Washout Period (7-14 Days)
COMPLETED
|
0
|
7
|
2
|
5
|
6
|
4
|
6
|
|
First Washout Period (7-14 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Second Intervention Period (12-16 Days)
STARTED
|
0
|
7
|
2
|
5
|
6
|
4
|
6
|
|
Second Intervention Period (12-16 Days)
COMPLETED
|
0
|
6
|
1
|
5
|
6
|
4
|
6
|
|
Second Intervention Period (12-16 Days)
NOT COMPLETED
|
0
|
1
|
1
|
0
|
0
|
0
|
0
|
|
Second Washout Period (7-14 Days)
STARTED
|
0
|
6
|
1
|
5
|
6
|
4
|
6
|
|
Second Washout Period (7-14 Days)
COMPLETED
|
0
|
6
|
1
|
5
|
6
|
4
|
6
|
|
Second Washout Period (7-14 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Third Intervention Period (12-16 Days)
STARTED
|
0
|
6
|
1
|
5
|
6
|
4
|
6
|
|
Third Intervention Period (12-16 Days)
COMPLETED
|
0
|
5
|
1
|
4
|
6
|
4
|
6
|
|
Third Intervention Period (12-16 Days)
NOT COMPLETED
|
0
|
1
|
0
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Metformin Run-in
Sponsor-provided, open-label metformin was administered from the run-in visit to the follow-up visit, inclusive, and it was provided as 500 milligram (mg) immediate-release tablets.
|
PF-04937319 150+100mg Then PF-04937319 300mg Then Sitagliptin
Participants received the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day and the second dose (PF-04937319 100mg) was taken with the lunch meal 5±1 hours after the morning dose, each day, for 14±2 days in the first intervention period; and then received the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the second intervention period; and then received the morning dose of sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the third intervention period.
|
PF-04937319 150+100mg Then Sitagliptin Then PF-04937319 300mg
Participants received the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day and the second dose (PF-04937319 100mg) was taken with the lunch meal 5±1 hours after the morning dose, each day, for 14±2 days in the first intervention period; and then received the morning dose of sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the second intervention period; and then received the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the third intervention period.
|
PF-04937319 300mg Then PF-04937319 150+100mg Then Sitagliptin
Participants received the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the first intervention period; and then received the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day and the second dose (PF-04937319 100mg) was taken with the lunch meal 5±1 hours after the morning dose, each day, for 14±2 days in the second intervention period; and then received the morning dose of sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days.
|
PF-04937319 300mg Then Sitagliptin Then PF-04937319 150+100mg
Participants received the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the first intervention period; and then received the morning dose of sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the second intervention period; and then received the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day and the second dose (PF-04937319 100mg) was taken with the lunch meal 5±1 hours after the morning dose, each day, for 14±2 days in the first intervention period.
|
Sitagliptin Then PF-04937319 150+100mg Then PF-04937319 300mg
Participants received the morning dose of sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the first intervention period; and then received the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day and the second dose (PF-04937319 100mg) was taken with the lunch meal 5±1 hours after the morning dose, each day, for 14±2 days in the second intervention period; and then received the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the third intervention period.
|
Sitagliptin Then PF-04937319 300mg Then PF-04937319 150+100mg
Participants received the morning dose of sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the first intervention period; and then received the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day, and the second dose of the study medication (placebo) was taken with the lunch meal 5±1 hours after the morning dose each day for 14±2 days in the second intervention period; and then received the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day and the second dose (PF-04937319 100mg) was taken with the lunch meal 5±1 hours after the morning dose, each day, for 14±2 days in the third intervention period.
|
|---|---|---|---|---|---|---|---|
|
Metformin Run-in Period
Adverse Event
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Metformin Run-in Period
No longer meets eligibility criteria
|
4
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Metformin Run-in Period
Other
|
5
|
0
|
0
|
0
|
0
|
0
|
0
|
|
First Intervention Period (12-16 Days)
Lost to Follow-up
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
First Intervention Period (12-16 Days)
Other
|
0
|
0
|
1
|
0
|
0
|
1
|
0
|
|
Second Intervention Period (12-16 Days)
Other
|
0
|
1
|
1
|
0
|
0
|
0
|
0
|
|
Third Intervention Period (12-16 Days)
Lost to Follow-up
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Third Intervention Period (12-16 Days)
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Study Of Two Dosing Regimens Of PF-04937319 Compared To An Approved Agent (Sitagliptin) In Patients With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
All*
n=33 Participants
A total of 90 participants with T2DM were consented for this study; of these, 43 transitioned into run-in with Sponsor-provided metformin and a total of 33 participants were randomized.
|
|---|---|
|
Age, Continuous
|
56.5 years
STANDARD_DEVIATION 8.3 • n=93 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Prior to morning dose (Hour 0) and at 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16, 20, and 24 hours post morning dose on Days 0 (baseline) and Day 14Population: Full analysis set defined as all randomized subjects who had taken at least 1 dose of blinded study medication and who had both a baseline and a post-baseline WMDG assessment. Number of participants analyzed was the evaluable participants with a measurement at both baseline and on Day 14.
Plasma glucose concentration was determined predose (Hour 0) and at 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16, 20, and 24 hours postdose on Days 0 (baseline) and 14. WMDG was calculated as the area under the curve (AUC) of the 12-point plasma glucose concentration-time profile divided by 24 hours.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=29 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
n=25 Participants
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Change From Baseline in Weighted Mean Daily Glucose (WMDG) at Day 14
|
-31.24 milligram/deciliter (mg/dL)
Standard Error 3.952
|
-31.33 milligram/deciliter (mg/dL)
Standard Error 4.604
|
-19.24 milligram/deciliter (mg/dL)
Standard Error 4.437
|
—
|
SECONDARY outcome
Timeframe: Day 14Population: Full analysis set defined as all randomized subjects who had taken at least 1 dose of blinded study medication and who had both a baseline and a post-baseline WMDG assessment. Number of participants analyzed was the evaluable participants with a measurement on Day 14.
Blood samples for measurement of glucose to permit derivation of pre-meal collections at the pre-specified nominal timepoints of each period: predose (ie, time "0"), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16 and 20 hours on Day 0 (baseline) and Day 14; and predose on Days 1 and 15.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
n=26 Participants
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14
|
-21.92 mg/dL
Standard Error 3.909
|
-20.70 mg/dL
Standard Error 4.324
|
-16.51 mg/dL
Standard Error 4.419
|
—
|
SECONDARY outcome
Timeframe: Day 14Population: Full analysis set defined as all randomized subjects who had taken at least 1 dose of blinded study medication and who had both a baseline and a post-baseline WMDG assessment. Number of participants analyzed was the evaluable participants with a measurement on Day 14.
Blood samples for measurement of glucose to permit derivation of pre-meal collections of blood samples for C-peptide at the pre-specified nominal timepoints at predose, 5 and 11 hours on Day 0 (baseline) and Day 14.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
n=26 Participants
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Change From Baseline in Pre-meal C-Peptide on Day 14
Pre-breakfast change from baseline
|
-0.06 nanograms/milliliter (ng/mL)
Standard Error 0.101
|
0.06 nanograms/milliliter (ng/mL)
Standard Error 0.115
|
0.30 nanograms/milliliter (ng/mL)
Standard Error 0.112
|
—
|
|
Change From Baseline in Pre-meal C-Peptide on Day 14
Pre-lunch change from baseline
|
0.20 nanograms/milliliter (ng/mL)
Standard Error 0.218
|
0.70 nanograms/milliliter (ng/mL)
Standard Error 0.249
|
0.06 nanograms/milliliter (ng/mL)
Standard Error 0.242
|
—
|
|
Change From Baseline in Pre-meal C-Peptide on Day 14
Pre-dinner change from baseline
|
0.36 nanograms/milliliter (ng/mL)
Standard Error 0.251
|
0.30 nanograms/milliliter (ng/mL)
Standard Error 0.289
|
0.32 nanograms/milliliter (ng/mL)
Standard Error 0.280
|
—
|
SECONDARY outcome
Timeframe: Day 14Population: Full analysis set defined as all randomized subjects who had taken at least 1 dose of blinded study medication and who had both a baseline and a post-baseline WMDG assessment. Number of participants analyzed was the evaluable participants with a measurement on Day 14.
Blood samples for measurement of glucose to permit derivation of pre-meal collections of blood samples for insulin at 0, 5 and 11 hours on Day 0 (baseline) and Day 14.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
n=26 Participants
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Change From Baseline in Pre-meal Insulin on Day 14
Pre-breakfast (n=31,30,26)
|
0.16 micro international unit/milliliter
Standard Error 0.704
|
0.46 micro international unit/milliliter
Standard Error 0.810
|
1.60 micro international unit/milliliter
Standard Error 0.793
|
—
|
|
Change From Baseline in Pre-meal Insulin on Day 14
Pre-lunch (n=30,27,25)
|
1.69 micro international unit/milliliter
Standard Error 1.690
|
4.07 micro international unit/milliliter
Standard Error 1.939
|
-0.01 micro international unit/milliliter
Standard Error 1.864
|
—
|
|
Change From Baseline in Pre-meal Insulin on Day 14
Pre-dinner (n=30,28,24)
|
-0.70 micro international unit/milliliter
Standard Error 2.286
|
5.06 micro international unit/milliliter
Standard Error 2.597
|
3.42 micro international unit/milliliter
Standard Error 2.714
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to Day 14Population: The safety analysis set was all participants who received at least one dose of randomized study treatment. HAEs meeting protocol definition were summarized descriptively by treatment.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=43 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
n=30 Participants
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
n=30 Participants
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%)
Participants evaluable for AEs
|
43 participants
|
31 participants
|
30 participants
|
30 participants
|
|
Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%)
Participants with AEs having a frequency rate >5%
|
3 participants
|
16 participants
|
19 participants
|
12 participants
|
|
Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%)
Participants with hypoglycaemia
|
2 participants
|
11 participants
|
14 participants
|
4 participants
|
|
Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%)
Participants with Headache
|
0 participants
|
4 participants
|
4 participants
|
4 participants
|
|
Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%)
Participants with Back pain
|
0 participants
|
2 participants
|
1 participants
|
2 participants
|
|
Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%)
Participants with Diarrhoea
|
1 participants
|
0 participants
|
2 participants
|
2 participants
|
|
Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%)
Participants with Musculoskeletal pain
|
0 participants
|
1 participants
|
2 participants
|
1 participants
|
|
Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%)
Participants with Pain in extremity
|
0 participants
|
1 participants
|
2 participants
|
1 participants
|
|
Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%)
Participants with Cough
|
0 participants
|
1 participants
|
0 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Day 1 up to Day 14Population: The safety analysis set was all participants who received at least one dose of randomized study treatment.
The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
n=27 Participants
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group
Total neutrophils (abs) (10^3/mm^3) <0.8 × LLN
|
1 participants
|
0 participants
|
0 participants
|
—
|
|
Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group
Eosinophils (abs) (10^3/mm^3) >1.2 × ULN
|
0 participants
|
0 participants
|
1 participants
|
—
|
|
Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group
Triglycerides (mg/dL) >1.3 × ULN
|
2 participants
|
0 participants
|
2 participants
|
—
|
|
Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group
Phosphate (mg/dL)<0.8 × LLN
|
1 participants
|
0 participants
|
0 participants
|
—
|
|
Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group
Glucose (mg/dL)>1.5 × ULN
|
16 participants
|
12 participants
|
14 participants
|
—
|
|
Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group
Creatine kinase (U/L) >2.0 × ULN
|
1 participants
|
1 participants
|
0 participants
|
—
|
|
Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group
Urine glucose (qual) ≥1
|
8 participants
|
4 participants
|
5 participants
|
—
|
|
Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group
Urine nitrite ≥1
|
2 participants
|
3 participants
|
1 participants
|
—
|
|
Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group
Urine leukocyte esterase ≥1
|
1 participants
|
1 participants
|
2 participants
|
—
|
|
Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group
Urine WBC (/HPF) ≥20
|
1 participants
|
1 participants
|
1 participants
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to Day 14Population: The safety analysis set was all participants who received at least one dose of randomized study treatment.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
n=26 Participants
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Change From Baseline in Body Weight (kg)
|
0.50 kg
Standard Error 0.313
|
0.30 kg
Standard Error 0.545
|
0.05 kg
Standard Error 0.215
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to Day 14Population: The safety analysis set was all participants who received at least one dose of randomized study treatment.
Vital signs included blood pressure (BP; supine, sitting and standing) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: sitting systolic BP (SBP) greater than or equal to (\>=) 30 millimeters of mercury (mm Hg) change from baseline, sitting SBP =\<20 mmHg change from baseline, supine/sitting/standing SBP less than (\<) 90 mm Hg; sitting diastolic BP (DBP) \>=20 mm Hg change from baseline, sitting SBP =\<20 mmHg change from baseline, supine/sitting/standing DBP \<50 mm Hg; 2), pulse rate (supine): \<40 or greater than (\>) 120 beats per minute (bpm).
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
n=29 Participants
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern
Sitting SBP <90 mm Hg
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern
Sitting DBP <50 mm Hg
|
0 participants
|
0 participants
|
1 participants
|
—
|
|
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern
Sitting Pulse Rate <40 bpm
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern
Sitting Pulse Rate >120 bpm
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern
Increase:sitting SBP≥30 mm Hg
|
1 participants
|
1 participants
|
2 participants
|
—
|
|
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern
Increase:sitting DBP≥20 mm Hg
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern
Decrease:sitting SBP≥30 mm Hg
|
2 participants
|
2 participants
|
2 participants
|
—
|
|
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern
Decrease:sitting DBP≥30 mm Hg
|
0 participants
|
0 participants
|
2 participants
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to Day 14Population: The safety analysis set was all participants who received at least one dose of randomized study treatment.
ECG criteria of potential clinical concern were 1), PR interval: \>=300 milliseconds (msec); \>=25% increase when baseline \>200 msec; or increase \>=50% when baseline \<=200 msec; 2), QRS interval: \>=140 msec; \>=50% increase from baseline; 3), QTc interval using Fridericia's formula (QTcF interval): absolute value \>=450 - \<480 msec, \>=480-\<500 msec, \>500 msec; absolute change 30 - \<60, \>=60 msec.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
n=29 Participants
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern
QTcF increase >=60 msec, n=31,30,29
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern
PR interval >=300 msec, n=31,30,29
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern
QRS interval >=140 msec, n=31,30,29
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern
QTcF interval 450-480 msec, n=31,30,29
|
2 participants
|
1 participants
|
1 participants
|
—
|
|
Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern
QTcF interval 480-500 msec, n=31,30,29
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern
QTcF interval >=500 msec, n=31,30,29
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern
PR interval increase >=25%/50%, n=31,30,29
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern
QRS interval increase >=50%, n=31,30,29
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern
QTcF increase 30-60 msec, n=31,30,29
|
0 participants
|
0 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15.Population: The PK population was defined as all randomized participants who received at least 1 dose of PF 04937319 and who had at least 1 PK sample with reported concentration.
The PK parameters were summarized descriptively by treatment as appropriate. Two (2) PK parameters specified in the protocol and SAP were not reported: AUClast was not reported since it was the same as AUC24 in this study, and apparent volume of distribution (Vz/F) was not reported since the log-linear terminal phase of the concentration-time profiles was not consistently well characterized in the 24-hour sampling period.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Plasma PF-04937319 Area Under the Concentration Time Curve From Time 0 to 24 Hours (AUC24) of PF-04937319 at Day 14
|
10710 ng•hr/mL
Geometric Coefficient of Variation 43
|
11810 ng•hr/mL
Geometric Coefficient of Variation 47
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15.Population: The PK population was defined as all randomized participants who received at least 1 dose of PF 04937319 and who had at least 1 PK sample with reported concentration.
The PK parameters were summarized descriptively by treatment as appropriate. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Plasma PF-04937319 Apparent Clearance (CL/F) on Day 14
|
389.2 mL/min
Geometric Coefficient of Variation 43
|
423.3 mL/min
Geometric Coefficient of Variation 47
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15.Population: The PK population was defined as all randomized participants who received at least 1 dose of PF 04937319 and who had at least 1 PK sample with reported concentration.
Cav was average concentration over the 24-hour period. The PK parameters were summarized descriptively by treatment as appropriate.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Plasma PF-04937319 Average Concentration Over the 24-hour Period (Cav) on Day 14
|
446.1 ng/mL
Geometric Coefficient of Variation 43
|
492.0 ng/mL
Geometric Coefficient of Variation 47
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15.Population: The PK population was defined as all randomized participants who received at least 1 dose of PF 04937319 and who had at least 1 PK sample with reported concentration.
Cmax was highest observed concentration. The PK parameters were summarized descriptively by treatment as appropriate.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Plasma PF-04937319 Highest Observed Concentration (Cmax) on Day 14
|
776.6 ng/mL
Geometric Coefficient of Variation 39
|
980.5 ng/mL
Geometric Coefficient of Variation 38
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15.Population: The PK population was defined as all randomized participants who received at least 1 dose of PF 04937319 and who had at least 1 PK sample with reported concentration.
Cmin lowest observed concentration during the 24-hour period. The PK parameters were summarized descriptively by treatment as appropriate.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Plasma PF-04937319 Lowest Observed Concentration During the 24-hour Period (Cmin) on Day 14
|
101.9 ng/mL
Geometric Coefficient of Variation 602
|
131.0 ng/mL
Geometric Coefficient of Variation 265
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15.Population: The PK population was defined as all randomized participants who received at least 1 dose of PF 04937319 and who had at least 1 PK sample with reported concentration.
Tmax was time of maximum concentration. The PK parameters were summarized descriptively by treatment as appropriate.
Outcome measures
| Measure |
PF-04937319 Split-Dose (150+100 mg)
n=31 Participants
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 Once-Daily (300 mg)
n=30 Participants
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Plasma PF-04937319 Time for Cmax (Tmax) on Day 14
|
6.50 hour
Full Range 602 • Interval 3.0 to 11.0
|
5.00 hour
Full Range 265 • Interval 1.5 to 12.5
|
—
|
—
|
Adverse Events
Metformin Run-in
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
PF-04937319 150+100 mg (Split Dose)
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
PF-04937319 300 mg (Once Daily)
Serious events: 0 serious events
Other events: 19 other events
Deaths: 0 deaths
Sitagliptin 100 mg
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Metformin Run-in
n=43 participants at risk
Sponsor-provided, open-label metformin was administered from the run-in visit to the follow-up visit, inclusive, and it was provided as 500 mg immediate-release tablets.
|
PF-04937319 150+100 mg (Split Dose)
n=31 participants at risk
Participants were instructed to take the morning dose of PF-04937319 150 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (PF-04937319 100 mg) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
PF-04937319 300 mg (Once Daily)
n=30 participants at risk
Participants were instructed to take the morning dose of PF-04937319 300 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication (placebo) should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
Sitagliptin 100 mg
n=30 participants at risk
Participants were instructed to take the morning dose of Sitagliptin 100 mg and at least 1 dose of open label metformin at the same time of day with the morning meal each day. In addition, the second dose of the study medication ()placebo should have been taken with the lunch meal approximately 5±1 hours after the morning dose, each day, for 14±2 days.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
2.3%
1/43
|
0.00%
0/31
|
6.7%
2/30
|
6.7%
2/30
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
4.7%
2/43
|
35.5%
11/31
|
46.7%
14/30
|
13.3%
4/30
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/43
|
6.5%
2/31
|
3.3%
1/30
|
6.7%
2/30
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/43
|
3.2%
1/31
|
6.7%
2/30
|
3.3%
1/30
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/43
|
3.2%
1/31
|
6.7%
2/30
|
3.3%
1/30
|
|
Nervous system disorders
Headache
|
0.00%
0/43
|
12.9%
4/31
|
13.3%
4/30
|
13.3%
4/30
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/43
|
3.2%
1/31
|
0.00%
0/30
|
6.7%
2/30
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER