Trial Outcomes & Findings for Sitagliptin Metformin/PPARg Agonist Combination Therapy Add-on (0431-052) (NCT NCT00350779)
NCT ID: NCT00350779
Last Updated: 2017-05-12
Results Overview
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
262 participants
Primary outcome timeframe
Baseline and 18 Weeks
Results posted on
2017-05-12
Participant Flow
Phase III First Patient In: 29-Aug-06. Last Patient Enrolled: 23-Mar-07. Last Patient Last Visit: 27-May-08; 41 study centers worldwide
Patients 18-78 years of age with T2DM and inadequate glycemic control (HbA1c ≥7.5 and ≤11.0%) who were on stable doses of rosiglitazone (≥4 mg/day) and metformin (≥1500 mg/day) after an up to 20-week dose-titration and stabilization period were eligible to enter the 54-week study.
Participant milestones
| Measure |
Sitagliptin 100 mg
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
The Placebo group includes data from patients randomized to receive treatment with placebo to sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Overall Study
STARTED
|
170
|
92
|
|
Overall Study
COMPLETED
|
148
|
71
|
|
Overall Study
NOT COMPLETED
|
22
|
21
|
Reasons for withdrawal
| Measure |
Sitagliptin 100 mg
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
The Placebo group includes data from patients randomized to receive treatment with placebo to sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
2
|
|
Overall Study
Lack of Efficacy
|
0
|
4
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
|
Overall Study
Physician Decision
|
2
|
4
|
|
Overall Study
Protocol Violation
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
9
|
8
|
|
Overall Study
Patient Moved
|
2
|
1
|
|
Overall Study
Non-compliance with study procedures
|
0
|
1
|
Baseline Characteristics
Sitagliptin Metformin/PPARg Agonist Combination Therapy Add-on (0431-052)
Baseline characteristics by cohort
| Measure |
Sitagliptin 100 mg
n=170 Participants
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=92 Participants
The Placebo group includes data from patients randomized to receive treatment with placebo to sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Total
n=262 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.4 years
STANDARD_DEVIATION 8.8 • n=99 Participants
|
54.8 years
STANDARD_DEVIATION 9.5 • n=107 Participants
|
54.5 years
STANDARD_DEVIATION 9.0 • n=206 Participants
|
|
Sex: Female, Male
Female
|
74 Participants
n=99 Participants
|
37 Participants
n=107 Participants
|
111 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
96 Participants
n=99 Participants
|
55 Participants
n=107 Participants
|
151 Participants
n=206 Participants
|
|
Race/Ethnicity
White
|
82 participants
n=99 Participants
|
51 participants
n=107 Participants
|
133 participants
n=206 Participants
|
|
Race/Ethnicity
Black
|
7 participants
n=99 Participants
|
3 participants
n=107 Participants
|
10 participants
n=206 Participants
|
|
Race/Ethnicity
Hispanic
|
13 participants
n=99 Participants
|
10 participants
n=107 Participants
|
23 participants
n=206 Participants
|
|
Race/Ethnicity
Asian
|
58 participants
n=99 Participants
|
24 participants
n=107 Participants
|
82 participants
n=206 Participants
|
|
Race/Ethnicity
Other
|
10 participants
n=99 Participants
|
4 participants
n=107 Participants
|
14 participants
n=206 Participants
|
|
HbA1c (Hemoglobin A1c)
|
8.8 Percent
STANDARD_DEVIATION 1.0 • n=99 Participants
|
8.7 Percent
STANDARD_DEVIATION 1.0 • n=107 Participants
|
8.8 Percent
STANDARD_DEVIATION 1.0 • n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline and 18 WeeksPopulation: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 18, the last non-baseline observed measurement was carried forward to Week 18.
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent.
Outcome measures
| Measure |
Sitagliptin 100 mg
n=168 Participants
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=88 Participants
The Placebo group includes data from patients randomized to receive treatment with placebo to sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18
|
-1.03 Percent
Interval -1.17 to -0.9
|
-0.31 Percent
Interval -0.5 to -0.13
|
SECONDARY outcome
Timeframe: Baseline and 18 WeeksPopulation: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 18, the last non-baseline observed measurement was carried forward to Week 18.
Change from baseline at Week 18 is defined as Week 18 minus Week 0
Outcome measures
| Measure |
Sitagliptin 100 mg
n=169 Participants
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=89 Participants
The Placebo group includes data from patients randomized to receive treatment with placebo to sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 18
|
-30.7 mg/dL
Interval -35.5 to -26.0
|
-11.7 mg/dL
Interval -18.3 to -5.1
|
SECONDARY outcome
Timeframe: Baseline and Week 18Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 18, the last non-baseline observed measurement was carried forward to Week 18.
Change from baseline at Week 18 is defined as Week 18 minus Week 0
Outcome measures
| Measure |
Sitagliptin 100 mg
n=142 Participants
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=75 Participants
The Placebo group includes data from patients randomized to receive treatment with placebo to sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 18
|
-59.9 mg/dL
Interval -67.1 to -52.6
|
-22.0 mg/dL
Interval -32.1 to -12.0
|
SECONDARY outcome
Timeframe: Baseline and Week 54Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 54, the last non-baseline observed measurement was carried forward to Week 54.
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent.
Outcome measures
| Measure |
Sitagliptin 100 mg
n=168 Participants
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=88 Participants
The Placebo group includes data from patients randomized to receive treatment with placebo to sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54
|
-1.05 Percent
Interval -1.21 to -0.89
|
-0.28 Percent
Interval -0.5 to -0.05
|
SECONDARY outcome
Timeframe: Baseline and Week 54Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 54, the last non-baseline observed measurement was carried forward to Week 54.
Change from baseline at Week 54 is defined as Week 54 minus Week 0
Outcome measures
| Measure |
Sitagliptin 100 mg
n=169 Participants
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=89 Participants
The Placebo group includes data from patients randomized to receive treatment with placebo to sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54
|
-28.0 mg/dL
Interval -33.3 to -22.8
|
-10.7 mg/dL
Interval -18.0 to -3.3
|
SECONDARY outcome
Timeframe: Baseline and Week 54Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 54, the last non-baseline observed measurement was carried forward to Week 54.
Change from baseline at Week 54 is defined as Week 54 minus Week 0.
Outcome measures
| Measure |
Sitagliptin 100 mg
n=147 Participants
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo
n=77 Participants
The Placebo group includes data from patients randomized to receive treatment with placebo to sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
|---|---|---|
|
Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54
|
-50.7 mg/dL
Interval -59.1 to -42.4
|
-16.6 mg/dL
Interval -28.2 to -5.0
|
Adverse Events
Sitagliptin 100 mg Data Through Week 18
Serious events: 2 serious events
Other events: 20 other events
Deaths: 0 deaths
Placebo Data Through Week 18
Serious events: 2 serious events
Other events: 14 other events
Deaths: 0 deaths
Sitagliptin 100 mg Data Through Week 54
Serious events: 14 serious events
Other events: 70 other events
Deaths: 0 deaths
Placebo Data Through Week 54
Serious events: 4 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sitagliptin 100 mg Data Through Week 18
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo Data Through Week 18
The Placebo group includes data from patients randomized to receive treatment with placebo to sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Sitagliptin 100 mg Data Through Week 54
|
Placebo Data Through Week 54
|
|---|---|---|---|---|
|
Cardiac disorders
Any Cardiac Disorders
|
0.00%
0/170
|
0.00%
0/92
|
1.2%
2/170
|
0.00%
0/92
|
|
Cardiac disorders
Myocardial Infarction
|
0.00%
0/170
|
0.00%
0/92
|
1.2%
2/170
|
0.00%
0/92
|
|
Ear and labyrinth disorders
Any Ear And Labyrinth Disorders
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
|
Hepatobiliary disorders
Any Hepatobiliary Disorders
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
|
Hepatobiliary disorders
Biliary Colic
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
|
Infections and infestations
Any Infections And Infestations
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
|
Injury, poisoning and procedural complications
Any Injury, Poisoning And Procedural Complications
|
0.00%
0/170
|
0.00%
0/92
|
0.00%
0/170
|
1.1%
1/92
|
|
Injury, poisoning and procedural complications
Lower Limb Fracture
|
0.00%
0/170
|
0.00%
0/92
|
0.00%
0/170
|
1.1%
1/92
|
|
Musculoskeletal and connective tissue disorders
Any Musculoskeletal And Connective Tissue Disorders
|
0.59%
1/170
|
0.00%
0/92
|
1.8%
3/170
|
0.00%
0/92
|
|
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion
|
0.59%
1/170
|
0.00%
0/92
|
1.2%
2/170
|
0.00%
0/92
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Any Neoplasms Benign, Malignant And Unspecified
|
0.00%
0/170
|
1.1%
1/92
|
2.4%
4/170
|
2.2%
2/92
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Astrocytoma Malignant
|
0.00%
0/170
|
0.00%
0/92
|
0.00%
0/170
|
1.1%
1/92
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
|
0.00%
0/170
|
1.1%
1/92
|
0.59%
1/170
|
1.1%
1/92
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neurilemmoma
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
|
Nervous system disorders
Any Nervous System Disorders
|
0.00%
0/170
|
0.00%
0/92
|
1.2%
2/170
|
0.00%
0/92
|
|
Nervous system disorders
Cerebrovascular Accident
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
|
Nervous system disorders
Diabetic Neuropathy
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
|
Psychiatric disorders
Any Psychiatric Disorders
|
0.00%
0/170
|
1.1%
1/92
|
0.00%
0/170
|
1.1%
1/92
|
|
Psychiatric disorders
Suicidal Ideation
|
0.00%
0/170
|
1.1%
1/92
|
0.00%
0/170
|
1.1%
1/92
|
|
Renal and urinary disorders
Any Renal And Urinary Disorders
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
|
Renal and urinary disorders
Renal Colic
|
0.00%
0/170
|
0.00%
0/92
|
0.59%
1/170
|
0.00%
0/92
|
Other adverse events
| Measure |
Sitagliptin 100 mg Data Through Week 18
The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Placebo Data Through Week 18
The Placebo group includes data from patients randomized to receive treatment with placebo to sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day).
|
Sitagliptin 100 mg Data Through Week 54
|
Placebo Data Through Week 54
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Any Gastrointestinal Disorders
|
0.00%
0/170
|
0.00%
0/92
|
4.7%
8/170
|
5.4%
5/92
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/170
|
0.00%
0/92
|
4.7%
8/170
|
5.4%
5/92
|
|
General disorders
Any General Disorders And Administration Site Conditions
|
0.00%
0/170
|
0.00%
0/92
|
8.8%
15/170
|
5.4%
5/92
|
|
General disorders
Oedema Peripheral
|
0.00%
0/170
|
0.00%
0/92
|
8.8%
15/170
|
5.4%
5/92
|
|
Infections and infestations
Any Infections And Infestations
|
11.8%
20/170
|
10.9%
10/92
|
27.1%
46/170
|
16.3%
15/92
|
|
Infections and infestations
Nasopharyngitis
|
5.9%
10/170
|
4.3%
4/92
|
10.6%
18/170
|
9.8%
9/92
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
5.9%
10/170
|
6.5%
6/92
|
16.5%
28/170
|
6.5%
6/92
|
|
Musculoskeletal and connective tissue disorders
Any Musculoskeletal And Connective Tissue Disorders
|
0.00%
0/170
|
5.4%
5/92
|
4.1%
7/170
|
5.4%
5/92
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/170
|
5.4%
5/92
|
4.1%
7/170
|
5.4%
5/92
|
|
Nervous system disorders
Any Nervous System Disorders
|
0.00%
0/170
|
0.00%
0/92
|
8.2%
14/170
|
8.7%
8/92
|
|
Nervous system disorders
Dizziness
|
0.00%
0/170
|
0.00%
0/92
|
3.5%
6/170
|
5.4%
5/92
|
|
Nervous system disorders
Headache
|
0.00%
0/170
|
0.00%
0/92
|
5.9%
10/170
|
4.3%
4/92
|
|
Nervous system disorders
Any Respiratory, Thoracic And Mediastinal Disorders
|
0.00%
0/170
|
0.00%
0/92
|
4.1%
7/170
|
7.6%
7/92
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/170
|
0.00%
0/92
|
4.1%
7/170
|
7.6%
7/92
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Email: [email protected]
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