A Multicenter, Randomized, Double-Blind Study of the Co-Administration of Sitagliptin and Pioglitazone in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control. - ND

• Register: EUCTR
• Last refreshed on: 18 April 2012
• Main ID: EUCTR2008-003640-11-IT
• Date of registration: 11/07/2008
• Prospective Registration: Yes
• Primary sponsor: MERCK & CO., INC.
• Public title: A Multicenter, Randomized, Double-Blind Study of the Co-Administration of Sitagliptin and Pioglitazone in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control. - ND
• Scientific title: A Multicenter, Randomized, Double-Blind Study of the Co-Administration of Sitagliptin and Pioglitazone in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control. - ND
• Date of first enrolment: 30/10/2008
• Target sample size: 1295
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-003640-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: yes Other specify the comparator: - same IMP used at different dosage

Countries of recruitment

Austria, Bulgaria, Estonia, Greece, Italy, Latvia, Lithuania, Slovenia

Key inclusion & exclusion criteria

Inclusion criteria:
At Visit 1
1. Patient has T2DM and is ≥18 and ≤ 78 years of age on day of signing informed
consent.
2. Patient is highly unlikely to conceive, as indicated by at least one "yes" answer to the following questions:
a. Patient is a male.
b. Patient is a surgically sterilized female.
Patient is not pregnant or breast feeding and is not intending to become pregnant
or donate eggs within the projected duration of the study and post-study follow-up
period.
d. Patient is a postmenopausal female ≥45 years of age with >2 years since last
menses.
e. Patient is a non-sterilized, premenopausal female and agrees to use adequate
contraception.
3. Patient understands the study procedures, alternative treatments available, and risks
involved with the study and voluntarily agrees to participate by giving informed
written consent.
Glycemic Entry Criteria
4. Patient is in one of the following 3 categories.
a. Patient is naïve to all AHA therapies (off all AHA therapies for at least 3 months
and not on an AHA for more than 4 weeks cumulatively in the last 3 years prior to
Visit 1) and has an HbA1c ≥7.5% and ≤11% on diet and exercise alone.
Or

Patient is in one of the following 2 non-naïve categories AND based upon review
of the patient?s current diet, medical regimen, and Visit 1/Screening HbA1c,
patient is considered likely to meet Visit 3 inclusion criterion of HbA1c ≥7.5% and
≤11.0%:
b. Patient is currently not on an AHA (i.e., off therapy for ≥8 weeks) and has a Visit
1/Screening Visit HbA1c ≥7.5% and ≤11.0% on diet and exercise alone.
c. Patient is currently on either metformin monotherapy or sulfonylurea
monotherapy and has a Visit 1/Screening Visit HbA1c ≥7% and ≤10.5%.
At Visit 3
5. HbA1c ≥7.5% and ≤11% at Visit 3 or measured within 2 weeks prior to Visit 3.
At Visit 4
6. Patient has ≥85% compliance with placebo treatment during the single-blind run-in,
as measured by site performed tablet count (e.g., for a patient with a 14-day interval
between Visit 3 and Visit 4, at least 12 tablets taken per bottle).
b. Patient is a surgically sterilized female.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
At Visit 1
Glucose Metabolism and Therapy Criteria
1. Patient has a history of type 1 diabetes mellitus or history of ketoacidosis or patient
has a C-peptide ≤0.8 ng/mL (0.26 nmol/L). Note: Only patients assessed by the
investigator as possibly having type 1 diabetes should have C-peptide measured at
Visit 1.
2. Patient has previously been treated with insulin, a thiazolidinedione (rosiglitazone or
pioglitazone), any DPP-4 inhibitor (sitagliptin, vildagliptin, saxagliptin or alogliptin),
exenatide, or has previously been in a clinical study with any DPP-4 inhibitor or
incretin mimetic.
NOTE: A patient who has received only minimal therapy with an excluded AHA
(e.g., <7 tablets of an oral AHA or brief insulin therapy during an acute illness) may
be considered for study participation after approval from the Merck Clinical Monitor.
Patients Requiring Specific Treatments
3. Patient is on a weight loss program and is not in the maintenance phase or has started
a weight loss medication (e.g. orlistat, phentermine, sibutramine or rimonabant)
within the prior 8 weeks.
4. Patient is on or is likely to require treatment with ≥14 consecutive days or repeated
courses of pharmacologic doses of corticosteroids.
Note: Inhaled, nasal, or topical corticosteroids are permitted.
5. Patient has received treatment with an investigational drug within 12 weeks prior to
Visit 1/Screening Visit or is currently participating in any other clinical study (drug
or non-drug studies).
6. Patient has undergone surgery within the prior 30 days or has major surgery planned during the study.
7. Patient has any contraindication to sitagliptin or pioglitazone based upon the label of the country of the investigational site.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control.
MedDRA version: 9.1 Level: LLT Classification code 10049746 Term: Insulin-requiring type II diabetes mellitus

Intervention(s)

Product Name: sitagliptin/pioglitazone
Product Code: MK0431C
Pharmaceutical Form: Tablet
Current Sponsor code: MK0431C
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Pharmaceutical Form: Tablet
INN or Proposed INN: SITAGLIPTIN
Current Sponsor code: MK0431
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Pioglitazone
Pharmaceutical Form: Tablet
INN or Proposed INN: Pioglitazone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Safety parameters and adverse experiences of special interest that are identified a priori (i.e., hypoglycemia, edema, and body weight) constitute "Tier 1" safety endpoints.

Main Objective: Objective: After 24 weeks, to assess the effect of the co-administration of sitagliptin and
pioglitazone compared with pioglitazone monotherapy and sitagliptin monotherapy on
HbA1c.
Hypothesis: After 24 weeks, the co-administration of sitagliptin and pioglitazone
provides greater reduction in HbA1c compared with pioglitazone monotherapy and
sitagliptin monotherapy.
Objective: After 24 and 54 weeks, to assess the safety and tolerability of the coadministration
of sitagliptin and pioglitazone compared with pioglitazone monotherapy
and sitagliptin monotherapy.
Hypothesis: After 24 and 54 weeks, the co-administration of sitagliptin and pioglitazone is well tolerated.

Secondary Objective: Objective: After 24 weeks, to assess the effect of the co-administration of sitagliptin and
pioglitazone compared with pioglitazone monotherapy and sitagliptin monotherapy on
fasting plasma glucose (FPG).
Hypothesis: After 24 weeks, the co-administration of sitagliptin and pioglitazone
provides greater reduction in FPG compared with pioglitazone monotherapy and
sitagliptin monotherapy.
Objective: After 24 weeks, to assess the effect of the co-administration of sitagliptin
and pioglitazone compared with pioglitazone monotherapy and sitagliptin monotherapy
on the 2-hour post meal glucose (PMG) following a standard meal challenge.
Hypothesis: After 24 weeks, the co-administration of sitagliptin and pioglitazone
provides greater reduction in 2-hour PMG following a standard meal challenge compared
with pioglitazone monotherapy and sitagliptin monotherapy.
Objective: After 54 weeks, to assess the effect of the co-administration of sitagliptin and pioglitazone compared with piogl

Secondary ID(s)

MK0431C-102