Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 diabetes mellitus, T2DM
Brief summary
This study will evaluate whether the addition of sitagliptin reduces hemoglobin A1C (A1C) more than the addition of placebo for participants with type 2 diabetes mellitus (T2DM) on a steady dose of acarbose. The primary hypothesis is that the addition of sitagliptin 100 mg once daily (q.d.) reduces A1C more than the addition of placebo in participants with T2DM with inadequate glycemic control on acarbose monotherapy.
Detailed description
The study includes an 8-week antihyperglycemic agent (AHA) wash-off period\* (which includes a 2-week single-blind placebo run-in period) followed by a 24-week double-blind treatment period. All participants will receive open-label acarbose at a minimum dose of 50 mg three times daily (t.i.d.) during the run-in and treatment periods. \*: Wash-off only applicable to patients who were on acarbose and another AHA.
Interventions
DRUGSitagliptin phosphate
Sitagliptin, 100 mg tablet once daily, orally for 24 weeks
DRUGComparator: Placebo
Placebo, to match sitagliptin tablet, once daily, orally for 24 weeks
DRUGAcarbose
Acarbose 50 mg or 100 mg tablet, 3 times daily, orally (continuing on the stable dose established prior to screening) for 24 weeks
DRUGGlimepiride
Participants not meeting specific glycemic goals during the study will use glimepiride as rescue therapy. For countries where glimepiride is not available, participants will receive a sulfonylurea marketed in that country as rescue therapy.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* has T2DM and is on acarbose alone at a stable dose of at least 50 mg t.i.d.(three times a day) for at least 10 weeks or on acarbose at a stable dose of at least 50 mg t.i.d. (three times a day) for at least 10 weeks in combination with another antihyperglycemic agent (AHA) * is at least 18 years of age (for participants in India: between 18 and 65 years of age) * male or female who is unlikely to conceive (not of reproductive potential, or agrees to remain abstinent or use \[or have partner use\] acceptable birth control if of reproductive potential)
Exclusion criteria
* has a history of type 1 diabetes mellitus * use of thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, or insulin * has the following cardiovascular disorders: acute coronary syndrome; new or worsening symptoms of coronary heart disease; coronary artery intervention; stroke or transient ischemic neurological disorder * has liver or kidney disease * has cancer or any clinically significant disease or disorder as judged by the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | Baseline and Week 24 | A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent. Efficacy analyses treated data as missing after the initiation of rescue therapy. |
| Number of Participants Who Experienced at Least One Adverse Event | Up to Week 24 + 14 Day Post-Study Follow-up | — |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | Up to 24 Weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline and Week 24 | Change from baseline at Week 24 is defined as Week 24 FPG minus Week 0 FPG. Efficacy analyses treated data as missing after the initiation of rescue therapy. |
Participant flow
Pre-assignment details
All participants randomized population. The participant flow module includes the second sequential randomization of a participant in the placebo group. Data for the second sequential randomization were excluded from the efficacy and safety analyses and the reason for not completed was a protocol violation.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin Sitagliptin 100 mg daily (q.d.) + acarbose (continuing the current stable dose of at least 50 mg three times daily \[t.i.d.\]) | 191 |
| Placebo Placebo q.d. + acarbose (continuing the current stable dose of at least 50 mg t.i.d.) | 189 |
| Total | 380 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 4 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 4 |
| Overall Study | Physician Decision | 0 | 3 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 12 |
Baseline characteristics
| Characteristic | Sitagliptin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56.5 Years STANDARD_DEVIATION 8.9 | 57.8 Years STANDARD_DEVIATION 9.5 | 57.1 Years STANDARD_DEVIATION 9.2 |
| Fasting plasma glucose | 177.3 mg/dL STANDARD_DEVIATION 37.5 | 177.5 mg/dL STANDARD_DEVIATION 40.2 | 177.4 mg/dL STANDARD_DEVIATION 38.8 |
| Hemoglobin A1c (A1C) | 8.09 Percent STANDARD_DEVIATION 0.79 | 8.08 Percent STANDARD_DEVIATION 0.9 | 8.08 Percent STANDARD_DEVIATION 0.85 |
| Sex: Female, Male Female | 94 Participants | 92 Participants | 186 Participants |
| Sex: Female, Male Male | 97 Participants | 97 Participants | 194 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 191 | 0 / 189 |
| serious Total, serious adverse events | 10 / 191 | 1 / 189 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (A1C) at Week 24
A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent. Efficacy analyses treated data as missing after the initiation of rescue therapy.
Time frame: Baseline and Week 24
Population: Full Analysis Set, all randomized participants except those who: failed to take at least 1 dose of study treatment, lacked all post-randomization data for the A1C subsequent to at least 1 dose of study treatment, or lacked baseline data for the A1C. Last observation carried forward (missing data approach).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | -0.76 Percent |
| Placebo | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | -0.14 Percent |
p-value: <0.00195% CI: [-0.79, -0.44]ANCOVA
Primary
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Time frame: Up to 24 Weeks
Population: All participants as treated population defined as all randomized participants who received at least one dose of study drug. Data were excluded after the initiation of rescue therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 5 Participants |
| Placebo | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 2 Participants |
Primary
Number of Participants Who Experienced at Least One Adverse Event
Time frame: Up to Week 24 + 14 Day Post-Study Follow-up
Population: All participants as treated population defined as all randomized participants who received at least one dose of study drug. Data were excluded after the initiation of rescue therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Number of Participants Who Experienced at Least One Adverse Event | 62 Participants |
| Placebo | Number of Participants Who Experienced at Least One Adverse Event | 58 Participants |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Change from baseline at Week 24 is defined as Week 24 FPG minus Week 0 FPG. Efficacy analyses treated data as missing after the initiation of rescue therapy.
Time frame: Baseline and Week 24
Population: Full Analysis Set, all randomized participants except those who: failed to take at least 1 dose of study treatment, lacked all post-randomization data for the FPG subsequent to at least 1 dose of study treatment, or lacked baseline data for the FPG. Last observation carried forward (missing data approach).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -17.9 mg/dL |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -3.5 mg/dL |
p-value: <0.00195% CI: [-21.8, -7]ANCOVA