Trial Outcomes & Findings for MK0431 (Sitagliptin) Pioglitazone Add-on Study for Patients With Type 2 Diabetes Mellitus (0431-055)(COMPLETED) (NCT NCT00372060)
NCT ID: NCT00372060
Last Updated: 2017-05-12
Results Overview
Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
134 participants
Primary outcome timeframe
12 Weeks
Results posted on
2017-05-12
Participant Flow
Phase III. Date of first patient in: 22 August 2006. Date of last patient's last visit for Period I: 1 May 2007. Date of last patient's last visit for Period II: 5 February 2008. Number of randomized patients: 134. The study was conducted at 32 centers in Japan.
Following a screening period of at least 4 weeks and a 2 or 8-week observation period, patients who were on pioglitazone monotherapy for at least 8 weeks and met all other entry criteria were randomized to receive: sitagliptin/sitagliptin or placebo/sitagliptin. The starting dose of sitagliptin was 50 mg for all patients.
Participant milestones
| Measure |
Sitagliptin / Sitagliptin
The Sitagliptin/Sitagliptin group includes data from all patients randomized to receive treatment with sitagliptin (Weeks 0-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
Placebo / Sitagliptin
The Placebo/Sitagliptin group includes data from all patients randomized to receive the sequence of placebo (Weeks 0-12) / sitagliptin (Weeks 12-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
|---|---|---|
|
Period I - Double-blind (Weeks 0-12)
STARTED
|
66
|
68
|
|
Period I - Double-blind (Weeks 0-12)
COMPLETED
|
63
|
67
|
|
Period I - Double-blind (Weeks 0-12)
NOT COMPLETED
|
3
|
1
|
|
Period II - Open-label (Weeks 12-52)
STARTED
|
63
|
67
|
|
Period II - Open-label (Weeks 12-52)
COMPLETED
|
49
|
59
|
|
Period II - Open-label (Weeks 12-52)
NOT COMPLETED
|
14
|
8
|
Reasons for withdrawal
| Measure |
Sitagliptin / Sitagliptin
The Sitagliptin/Sitagliptin group includes data from all patients randomized to receive treatment with sitagliptin (Weeks 0-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
Placebo / Sitagliptin
The Placebo/Sitagliptin group includes data from all patients randomized to receive the sequence of placebo (Weeks 0-12) / sitagliptin (Weeks 12-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
|---|---|---|
|
Period I - Double-blind (Weeks 0-12)
Adverse Event
|
2
|
0
|
|
Period I - Double-blind (Weeks 0-12)
Lack of Efficacy
|
0
|
1
|
|
Period I - Double-blind (Weeks 0-12)
No improvement in hyperglycemia
|
1
|
0
|
|
Period II - Open-label (Weeks 12-52)
Adverse Event
|
3
|
0
|
|
Period II - Open-label (Weeks 12-52)
Lack of Efficacy
|
9
|
8
|
|
Period II - Open-label (Weeks 12-52)
Withdrawal by Subject
|
2
|
0
|
Baseline Characteristics
MK0431 (Sitagliptin) Pioglitazone Add-on Study for Patients With Type 2 Diabetes Mellitus (0431-055)(COMPLETED)
Baseline characteristics by cohort
| Measure |
Total
n=134 Participants
Total of all reporting groups
|
Sitagliptin / Sitagliptin
n=66 Participants
The Sitagliptin/Sitagliptin group includes data from all patients randomized to receive treatment with sitagliptin (Weeks 0-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
Placebo / Sitagliptin
n=68 Participants
The Placebo/Sitagliptin group includes data from all patients randomized to receive the sequence of placebo (Weeks 0-12) / sitagliptin (Weeks 12-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
|---|---|---|---|
|
Age, Continuous
|
58.4 years
STANDARD_DEVIATION 9.5 • n=5 Participants
|
57.8 years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
59.0 years
STANDARD_DEVIATION 9.2 • n=7 Participants
|
|
Sex: Female, Male
Female
|
47 Participants
n=5 Participants
|
28 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
87 Participants
n=5 Participants
|
38 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
|
Fasting Plasma Glucose
|
149.1 mg/dL
STANDARD_DEVIATION 33.8 • n=5 Participants
|
146.8 mg/dL
STANDARD_DEVIATION 33.1 • n=5 Participants
|
151.3 mg/dL
STANDARD_DEVIATION 34.6 • n=7 Participants
|
|
Hemoglobin A1c (HbA1c)
|
7.7 Percent
STANDARD_DEVIATION 0.8 • n=5 Participants
|
7.7 Percent
STANDARD_DEVIATION 0.9 • n=5 Participants
|
7.6 Percent
STANDARD_DEVIATION 0.8 • n=7 Participants
|
PRIMARY outcome
Timeframe: 12 WeeksPopulation: Analysis in the Full Analysis Set with Last Observation Carried Forward (The Full Analysis Set population includes all randomized patients who took at least 1 dose of study medication and had both a baseline and at least one post-baseline value.)
Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication.
Outcome measures
| Measure |
Sitagliptin / Sitagliptin
n=66 Participants
The Sitagliptin/Sitagliptin group includes data from all patients randomized to receive treatment with sitagliptin (Weeks 0-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
Placebo / Sitagliptin
n=68 Participants
The Placebo/Sitagliptin group includes data from all patients randomized to receive the sequence of placebo (Weeks 0-12) / sitagliptin (Weeks 12-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
|---|---|---|
|
Change From Baseline in Hemoglobin A1c (HbA1c ) at Week 12
|
-0.4 Percent
Interval -0.6 to -0.3
|
0.4 Percent
Interval 0.3 to 0.5
|
SECONDARY outcome
Timeframe: 12 WeeksPopulation: Analysis in the Full Analysis Set with Last Observation Carried Forward (The Full Analysis Set population includes all randomized patients who took at least 1 dose of study medication and had both a baseline and at least one post-baseline value.)
Change from baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication.
Outcome measures
| Measure |
Sitagliptin / Sitagliptin
n=66 Participants
The Sitagliptin/Sitagliptin group includes data from all patients randomized to receive treatment with sitagliptin (Weeks 0-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
Placebo / Sitagliptin
n=68 Participants
The Placebo/Sitagliptin group includes data from all patients randomized to receive the sequence of placebo (Weeks 0-12) / sitagliptin (Weeks 12-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose at Week 12
|
-12.2 mg/dL
Interval -17.0 to -7.5
|
4.4 mg/dL
Interval -0.3 to 9.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 weeksPopulation: Analysis in the Full Analysis Set without Last Observation Carried Forward (The Full Analysis Set population includes all randomized patients who took at least 1 dose of study medication and had both a baseline and at least one post-baseline values.).
Change from baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication.
Outcome measures
| Measure |
Sitagliptin / Sitagliptin
n=63 Participants
The Sitagliptin/Sitagliptin group includes data from all patients randomized to receive treatment with sitagliptin (Weeks 0-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
Placebo / Sitagliptin
n=67 Participants
The Placebo/Sitagliptin group includes data from all patients randomized to receive the sequence of placebo (Weeks 0-12) / sitagliptin (Weeks 12-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
|---|---|---|
|
Change From Baseline in 2 Hour Postprandial Glucose at Week 12
|
-42.7 mg/dL
Interval -53.7 to -31.7
|
6.4 mg/dL
Interval -4.2 to 17.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 52 (reflecting change from Week 0) for Sitagliptin/Sitagliptin group; Weeks 52 (reflecting change from Week 12) for Placebo/Sitagliptin group.Population: The Completers Population (CP) includes all randomized patients who took at least 1 dose of sitagliptin and had \[1\] a baseline (Sitagliptin/Sitagliptin group) or Week 12 (Placebo/Sitagliptin group) value and \[2\] a value at Week 52.
Change from the last value before receiving sitagliptin therapy: Week 0 for Sitagliptin/Sitagliptin group and Week 12 for the Placebo/Sitagliptin group.
Outcome measures
| Measure |
Sitagliptin / Sitagliptin
n=50 Participants
The Sitagliptin/Sitagliptin group includes data from all patients randomized to receive treatment with sitagliptin (Weeks 0-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
Placebo / Sitagliptin
n=59 Participants
The Placebo/Sitagliptin group includes data from all patients randomized to receive the sequence of placebo (Weeks 0-12) / sitagliptin (Weeks 12-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40.
|
|---|---|---|
|
Change From Baseline in Hemoglobin A1c (HbA1c ) at Week 52
|
-0.6 Percent
Interval -0.8 to -0.5
|
-0.9 Percent
Interval -1.1 to -0.7
|
Adverse Events
Sitagliptin/Sitagliptin (Data Through Week 12)
Serious events: 3 serious events
Other events: 21 other events
Deaths: 0 deaths
Placebo/Sitagliptin (Data Through Week 12)
Serious events: 1 serious events
Other events: 23 other events
Deaths: 0 deaths
Pooled Sitagliptin (Data Through Week 52)
Serious events: 7 serious events
Other events: 80 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sitagliptin/Sitagliptin (Data Through Week 12)
The Sitagliptin/Sitagliptin group includes data from all patients randomized to receive treatment with sitagliptin orally once daily (Weeks 0-52). This column of data includes only Weeks 0-12.
|
Placebo/Sitagliptin (Data Through Week 12)
The Placebo/Sitagliptin group includes data from all patients randomized to receive the sequence of placebo (Weeks 0-12) / sitagliptin (Weeks 12-52) orally once daily. This column of data includes only Weeks 0-12.
|
Pooled Sitagliptin (Data Through Week 52)
The Pooled Sitagliptin group includes data from all patients who took sitagliptin in either treatment group. Includes data from Week 0 to Week 52 for patients in the Sitagliptin/Sitagliptin group and data from Week 12 to Week 52 for patients in the Placebo/Sitagliptin group. Includes patients (from either group) who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily.
|
|---|---|---|---|
|
Cardiac disorders
Coronary artery stenosis
|
1.5%
1/66
|
0.00%
0/68
|
0.75%
1/133
|
|
Infections and infestations
Enteritis infectious
|
0.00%
0/66
|
0.00%
0/68
|
0.75%
1/133
|
|
Injury, poisoning and procedural complications
Patella fracture
|
0.00%
0/66
|
0.00%
0/68
|
0.75%
1/133
|
|
Injury, poisoning and procedural complications
Pneumothorax traumatic
|
0.00%
0/66
|
0.00%
0/68
|
0.75%
1/133
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/66
|
0.00%
0/68
|
0.75%
1/133
|
|
Injury, poisoning and procedural complications
Ligament injury
|
0.00%
0/66
|
1.5%
1/68
|
0.00%
0/133
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/66
|
1.5%
1/68
|
0.00%
0/133
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant
|
0.00%
0/66
|
0.00%
0/68
|
0.75%
1/133
|
|
Nervous system disorders
Cerebral infarction
|
1.5%
1/66
|
0.00%
0/68
|
0.75%
1/133
|
|
Vascular disorders
Hypertension
|
1.5%
1/66
|
0.00%
0/68
|
0.75%
1/133
|
Other adverse events
| Measure |
Sitagliptin/Sitagliptin (Data Through Week 12)
The Sitagliptin/Sitagliptin group includes data from all patients randomized to receive treatment with sitagliptin orally once daily (Weeks 0-52). This column of data includes only Weeks 0-12.
|
Placebo/Sitagliptin (Data Through Week 12)
The Placebo/Sitagliptin group includes data from all patients randomized to receive the sequence of placebo (Weeks 0-12) / sitagliptin (Weeks 12-52) orally once daily. This column of data includes only Weeks 0-12.
|
Pooled Sitagliptin (Data Through Week 52)
The Pooled Sitagliptin group includes data from all patients who took sitagliptin in either treatment group. Includes data from Week 0 to Week 52 for patients in the Sitagliptin/Sitagliptin group and data from Week 12 to Week 52 for patients in the Placebo/Sitagliptin group. Includes patients (from either group) who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily.
|
|---|---|---|---|
|
Gastrointestinal disorders
Periodontitis
|
0.00%
0/66
|
0.00%
0/68
|
5.3%
7/133
|
|
Infections and infestations
Nasopharyngitis
|
16.7%
11/66
|
25.0%
17/68
|
36.1%
48/133
|
|
Investigations
Weight increased
|
3.0%
2/66
|
0.00%
0/68
|
7.5%
10/133
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
1.5%
1/66
|
0.00%
0/68
|
6.0%
8/133
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/66
|
2.9%
2/68
|
5.3%
7/133
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
13.6%
9/66
|
4.4%
3/68
|
14.3%
19/133
|
|
Investigations
Blood creatine phosphokinase increased
|
1.5%
1/66
|
2.9%
2/68
|
12.8%
17/133
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Results disclosure agreements
- Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER