Glucose Intolerance
Conditions
Brief summary
This study is being done to evaluate the safety, efficacy, and dose level of sitagliptin (MK-0431/ONO-5435) used once daily (qd) in Japanese participants with impaired glucose tolerance who have inadequate glycemic control using diet and exercise therapy.
Interventions
DRUGPlacebo for Sitagliptin 25 mg
1 tablet orally once daily before breakfast for 8 weeks
DRUGPlacebo for Sitagliptin 50 mg
1 tablet orally once daily before breakfast for 8 weeks
DRUGSitagliptin 25 mg
1 tablet orally once daily before breakfast for 8 weeks
1 tablet orally once daily before breakfast for 8 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Impaired glucose tolerance * On diet/exercise therapy * Unlikely to conceive * Meets all of the following glycemic parameters: Hemoglobin A1c (Japan Diabetes Society value) \<6.1%, Fasting Plasma Glucose \<126 mg/dL, and 2-hr plasma glucose level in 75g oral glucose tolerance test ≥140 mg/dL and \<200 mg/dL
Exclusion criteria
* History of diabetes mellitus * Disease or condition of clear or likely glucose tolerance disorder * Previously treated with a drug to prevent diabetes and/or any antihyperglycemic drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for Meal Tolerance Test (MTT) at Week 8 | Baseline (Week 0) and Week 8 | Glucose total AUC 0-2 hours for MTT was measured at Baseline (Week 0) and at Week 8. After fasting for ≥10 hours, blood samples for glucose measurement were drawn at 0 minutes (at standard meal loading), 30 minutes, 60 minutes, 90 minutes, and 120 minutes. At Week 8, participants received study drug or placebo 30 minutes prior to consuming a standard meal. |
| Percentage of Participants Who Experienced One or More Adverse Events (AEs) | Up to 10 weeks | An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. |
| Percentage of Participants Who Discontinued Treatment Due to an Adverse Event (AE) | Up to 8 weeks | An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for 75-gram Oral Glucose Tolerance Test (OGTT) at Week 7 | Baseline (Week -1) and Week 7 | Glucose total AUC 0-2 hours for 75 g OGTT was measured at Baseline (Week -1) and at Week 7. After fasting for ≥10 hours, blood samples for glucose measurement were drawn at 0 minutes (at 75 g glucose loading), 30 minutes, 60 minutes, 90 minutes, and 120 minutes. At Week 7, participants received study drug or placebo 30 minutes prior to loading 75 g glucose solution. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received one tablet of placebo for sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks. | 83 |
| Sitagliptin 25 mg Participants received one tablet of sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks. | 82 |
| Sitagliptin 50 mg Participants received one tablet of sitagliptin 50 mg and one tablet of placebo for sitagliptin 25 mg orally once daily for 8 weeks. | 77 |
| Total | 242 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Pre-treatment lab AE | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | Sitagliptin 25 mg | Sitagliptin 50 mg |
|---|---|---|---|---|
| Age, Continuous | 62.3 Years STANDARD_DEVIATION 9.8 | 61.9 Years STANDARD_DEVIATION 10.6 | 63.1 Years STANDARD_DEVIATION 9.5 | 61.9 Years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 105 Participants | 35 Participants | 38 Participants | 32 Participants |
| Sex: Female, Male Male | 137 Participants | 48 Participants | 44 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 81 | 0 / 82 | 0 / 78 |
| other Total, other adverse events | 13 / 81 | 14 / 82 | 11 / 78 |
| serious Total, serious adverse events | 0 / 81 | 0 / 82 | 0 / 78 |
Outcome results
Primary
Percentage of Participants Who Discontinued Treatment Due to an Adverse Event (AE)
An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time frame: Up to 8 weeks
Population: All randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the actual study treatment they received. Due to a prescription error, one participant who was randomized to the placebo group took sitagliptin 50 mg.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Discontinued Treatment Due to an Adverse Event (AE) | 0.0 Percentage of participants |
| Sitagliptin 25 mg | Percentage of Participants Who Discontinued Treatment Due to an Adverse Event (AE) | 0.0 Percentage of participants |
| Sitagliptin 50 mg | Percentage of Participants Who Discontinued Treatment Due to an Adverse Event (AE) | 0.0 Percentage of participants |
Primary
Percentage of Participants Who Experienced One or More Adverse Events (AEs)
An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time frame: Up to 10 weeks
Population: All randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the actual study treatment they received. Due to a prescription error, one participant who was randomized to the placebo group took sitagliptin 50 mg.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Experienced One or More Adverse Events (AEs) | 30.9 Percentage of participants |
| Sitagliptin 25 mg | Percentage of Participants Who Experienced One or More Adverse Events (AEs) | 34.1 Percentage of participants |
| Sitagliptin 50 mg | Percentage of Participants Who Experienced One or More Adverse Events (AEs) | 41.0 Percentage of participants |
Primary
Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for Meal Tolerance Test (MTT) at Week 8
Glucose total AUC 0-2 hours for MTT was measured at Baseline (Week 0) and at Week 8. After fasting for ≥10 hours, blood samples for glucose measurement were drawn at 0 minutes (at standard meal loading), 30 minutes, 60 minutes, 90 minutes, and 120 minutes. At Week 8, participants received study drug or placebo 30 minutes prior to consuming a standard meal.
Time frame: Baseline (Week 0) and Week 8
Population: All participants, as randomized, who received at least one dose of study treatment and have a baseline measurement or post-randomization measurement for the analysis endpoint subsequent to study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for Meal Tolerance Test (MTT) at Week 8 | -2.42 Percent change |
| Sitagliptin 25 mg | Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for Meal Tolerance Test (MTT) at Week 8 | -9.52 Percent change |
| Sitagliptin 50 mg | Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for Meal Tolerance Test (MTT) at Week 8 | -11.49 Percent change |
p-value: <0.00195% CI: [-9.85, -4.36]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [-11.82, -6.33]Constrained Longitudinal Data Analysis
p-value: 0.14395% CI: [-4.61, 0.67]Constrained Longitudinal Data Analysis
Secondary
Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for 75-gram Oral Glucose Tolerance Test (OGTT) at Week 7
Glucose total AUC 0-2 hours for 75 g OGTT was measured at Baseline (Week -1) and at Week 7. After fasting for ≥10 hours, blood samples for glucose measurement were drawn at 0 minutes (at 75 g glucose loading), 30 minutes, 60 minutes, 90 minutes, and 120 minutes. At Week 7, participants received study drug or placebo 30 minutes prior to loading 75 g glucose solution.
Time frame: Baseline (Week -1) and Week 7
Population: All participants, as randomized, who received at least one dose of study treatment and have a baseline measurement or post-randomization measurement for the analysis endpoint subsequent to study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for 75-gram Oral Glucose Tolerance Test (OGTT) at Week 7 | -3.68 Percent change |
| Sitagliptin 25 mg | Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for 75-gram Oral Glucose Tolerance Test (OGTT) at Week 7 | -21.38 Percent change |
| Sitagliptin 50 mg | Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for 75-gram Oral Glucose Tolerance Test (OGTT) at Week 7 | -20.09 Percent change |
p-value: <0.00195% CI: [-21.55, -13.86]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [-20.32, -12.5]Constrained Longitudinal Data Analysis
p-value: 0.46995% CI: [-2.22, 4.82]Constrained Longitudinal Data Analysis