A multicenter, randomized, open label, active-comparator controlled study to assess the efficacy, safety and tolerability of taspoglutide (RO5073031) compared to exenatide in patients with type 2 diabetes mellitus inadequately controlled with metformin, thiazolidinedione or a combination of both

• Register: EUCTR
• Last refreshed on: 12 June 2012
• Main ID: EUCTR2008-001856-36-GR
• Date of registration: 06/02/2009
• Prospective Registration: No
• Primary sponsor: F. Hoffmann- La Roche Ltd
• Public title: A multicenter, randomized, open label, active-comparator controlled study to assess the efficacy, safety and tolerability of taspoglutide (RO5073031) compared to exenatide in patients with type 2 diabetes mellitus inadequately controlled with metformin, thiazolidinedione or a combination of both
• Scientific title: A multicenter, randomized, open label, active-comparator controlled study to assess the efficacy, safety and tolerability of taspoglutide (RO5073031) compared to exenatide in patients with type 2 diabetes mellitus inadequately controlled with metformin, thiazolidinedione or a combination of both
• Date of first enrolment: 19/11/2008
• Target sample size: 990
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-001856-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Denmark, Finland, France, Germany, Greece, Italy, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Men and women aged 18 - 75 years at screening. Women of childbearing potential using two medically approved birth control methods (e.g. hormonal contraceptives, IUD, barrier contraception) must be willing to use the same methods of contraception during the whole course of the study.
2. Patients with type 2 diabetes on metformin > 1500 mg/day and/or pioglitazone = 30 mg/day or rosiglitazone = 4 mg/day (in the countries where the combination of thiazolidinediones and exenatide is approved) or the maximum dose specified in the label for all the above compounds on stable dose for at least 12 weeks, prior to screening.
3. HbA1c: = 7.0% and =10% at screening
4. Body mass index (BMI) = 25 (>23 for Asians) and = 45 kg/m2 at screening.
5. Stable weight ± 5% for at least 12 weeks prior to screening.
6. Agreement to maintain prior diet and exercise habits during the full course of the study.
7. Ability and willingness to give written informed consent and to comply with the requirements of the study.
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:
1. Women who are pregnant, intending to become pregnant during the study period or currently lactating females.
2. Diagnosis of or history of:
a. Type 1 diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes, e.g. acromegaly and Cushing’s syndrome.
b. Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma within the past 6 months.
3. Evidence of clinically significant diabetic complications.
4. Clinically symptomatic gastrointestinal (GI) disease including inflammatory bowel disease, celiac disease, diabetic gastroparesis.
5. History of gastric bypass or antrectomy or small bowel resection.
6. History of chronic pancreatitis or idiopathic acute pancreatitis.
7. Myocardial infarction (MI), coronary artery bypass surgery, post-transplantation cardiomyopathy (PTCM) or stroke within the past 6 months.
8. Any abnormality in clinical laboratory tests or ECG, which precludes safe involvement in the study as judged by the Investigator.
9. Clinically relevant QTc prolongation (e.g. QTc > 480 ms), family history of Long QT Syndrome, or concomitant use of Class I Antiarrythmic drugs (e.g. disopyramide, quinidine, procainamide, mexiletine, flecainide, propafenone).
10. Diagnosed and/or treated malignancy (except basal cell skin cancer, in situ carcinoma of the cervix, or in situ prostate cancer) within the past 5 years.
11. Known hemoglobinopathy or chronic anemia.
12. Donation of one unit (500 ml) or more blood, significant blood loss equaling to at least one unit of blood within the past 2 weeks or a blood transfusion within the past 8 weeks.
13. Any concurrent medical condition/disorder that, in the opinion of the Investigator is likely:
- to interfere with the patient’s ability to participate in all aspects of the trial,
- to require, during the study, the administration of a treatment that would affect the interpretation of the efficacy and safety data.
14. Contraindications and warnings according to the country specific label information for metformin, pioglitazone, rosiglitazone and exenatide not listed in the other exclusion criteria.
15. Known hypersensitivity to pioglitazone, rosiglitazone or metformin or any of their components.
16. Known hypersensitivity to exenatide or exendin analogues.
17. Treatment with any oral anti-diabetic medication (other than metformin, thiazolidinediones) and/or herbal/over-the-counter preparations that may affect glycemic control within 12 weeks prior to screening.
18. Treatment with exenatide or exendin analogues, GLP-1 or GLP-1 analogues at anytime during the past.
19. Treatment with insulin (except during pregnancy) for more than one week within 6 months prior to screening.
20. Chronic oral or parenteral corticosteroid treatment (>7 consecutive days of treatment) within 4 weeks prior to screening.
21. Treatment with weight lowering agents (e.g. orlistat, sibutramine, rimonabant, phentermine) during the last 12 weeks prior to screening.
22. History of unstable hypertension (SBP > 170 mmHg and/or DBP > 105 mmHg), within the past 12 weeks prior to screening.
23. Treatment with anti-hypertensive medications which are not on a stable dose for at least 4 weeks prior to Baseline.
24. Treatment with lipid lowering medications which are not on a stable dose for at least 8 weeks prior to screening.
25. Treatment with thyroid hormones which are not on a stable dose for at least 12 weeks prior to screening.
26. Use of investigational drugs within 30 days or 5

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

Health Condition(s) or Problem(s) studied

Type 2 diabetes mellitus
MedDRA version: 9.1 Level: LLT Classification code 10012601 Term: Diabetes mellitus

Intervention(s)

Product Name: Taspoglutide
Product Code: RO5073031
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Taspoglutide
CAS Number: 275371-94-3
Current Sponsor code: RO5073031
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Byetta
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Exenatide
CAS Number: 141758-74-9
Other descriptive name: Byetta
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Byetta
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Exenatide
CAS Number: 141758-74-9
Other descriptive name: Byetta
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 10-

Product Name: Taspoglutide
Product Code: RO5073031
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Taspoglutide
CAS Number: 275371-94-3
Current Sponsor code: RO5073031
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Main Objective: To assess the efficacy of taspoglutide based on glycemic control (as assessed by HbA1c) after 24 weeks of treatment in patients with type 2 diabetes mellitus inadequately controlled with metformin, thiazolidinedione or a combination of metformin and thiazolidinedione compared with exenatide BID.

Primary end point(s): The primary endpoint of the study is the absolute change from baseline in HbA1c (%) after 24 weeks (one week after last injection).

Secondary Objective: •Absolute/percentage change from baseline in fasting plasma glucose (FPG).
•Absolute/percentage change from baseline in body weight.
•Responder rates, defined as target HbA1c: = 7.0 %, = 6.5%.
•Beta cell function (indexed by fasting pro-insulin concentration, fasting pro-insulin/insulin ratio, HOMA-B).
•Meal test in a subset of patients: change in glucose, insulin, C-peptide, glucagon values (7 time-points over 3 hours).
•To assess the safety and tolerability of taspoglutide versus exenatide BID.
•To describe the pharmacokinetics of taspoglutide and to estimate between-patient variability using a population PK approach, exploring and quantifying the potential influence of covariates that contribute significantly to the between-patient differences in PK parameters of taspoglutide.

Secondary ID(s)

BC21625

2008-001856-36-IT