A multicenter, double-blind, randomized, active controlled, parallel group study to compare the effect of 12 weeks treatment with LAF237 50 mg BID to 50 mg OD in patients with type 2 diabetes with HbA1c 9-11%. 52 week extension to a multicenter, double-blind, randomized, active controlled, parallel group study to compare the effect of 12 weeks treatment with LAF237 50 mg BID to 50 mg OD in patients with type 2 diabetes with HbA1c 9-11%.

• Register: EUCTR
• Last refreshed on: 4 April 2022
• Main ID: EUCTR2004-002466-38-CZ
• Date of registration: 03/09/2004
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• Public title: A multicenter, double-blind, randomized, active controlled, parallel group study to compare the effect of 12 weeks treatment with LAF237 50 mg BID to 50 mg OD in patients with type 2 diabetes with HbA1c 9-11%. 52 week extension to a multicenter, double-blind, randomized, active controlled, parallel group study to compare the effect of 12 weeks treatment with LAF237 50 mg BID to 50 mg OD in patients with type 2 diabetes with HbA1c 9-11%.
• Scientific title: A multicenter, double-blind, randomized, active controlled, parallel group study to compare the effect of 12 weeks treatment with LAF237 50 mg BID to 50 mg OD in patients with type 2 diabetes with HbA1c 9-11%. 52 week extension to a multicenter, double-blind, randomized, active controlled, parallel group study to compare the effect of 12 weeks treatment with LAF237 50 mg BID to 50 mg OD in patients with type 2 diabetes with HbA1c 9-11%.
• Date of first enrolment: 01/11/2004
• Target sample size: 225
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-002466-38
• 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 Other trial design description: No If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic

Key inclusion & exclusion criteria

Inclusion criteria:
1.Drug nave patients with type 2 diabetes (drug naïve patients are defined as patients who have had no treatment with oral antidiabetic agents for at least 12 weeks prior to study entry (visit 1) and no treatment with oral antidiabetic agents for > 3 consecutive months at any time in the past).
2. Body mass index (BMI) in the range of 22-45 kg/m2 inclusive at visit 1.
3. HbA1c in the range of 9.0 to 11.0 % inclusive at visit 1.
4. Fasting C-peptide > 0.6 ng/ml (0.2 nmol/l) at visit 1.
5 Age = 18 year
6.Male, non-fertile female (i.e., post menopausal, post hysterectomy, or sterilized by tubal ligation) or female of childbearing potential using a non-hormonal medically approved birth control method (e.g., IUD, double-barrier contraception). Females using hormonal contraceptives must use a non-hormonal medically approved birth control method in addition during the full course of the study. A female of childbearing potential must be willing to use the same method(s) of contraception during the entire 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. Pregnant or lactating female.
2. A history of:
Type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g., Cushing’s syndrome and acromegaly.
Acute diabetic complication
3. Liver disease such as cirrhosis or chronic active hepatitis.
4. Congestive heart failure.
5. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1.
6. Acromegaly or treatment with growth hormone or similar drugs.
7. Any of the following ECG abnormalities:
12. Investigational drug treatment within 4 weeks prior to visit 1 unless local health authority guidelines mandate a longer period.
13. Treatment with any drug with a known and frequent toxicity to a major organ system within the past 3 months (i.e., cytostatic drugs).
14. Any of the following significant laboratory abnormalities:
ALT, AST greater than 2.5 times the upper limit of the normal range at visit 1.
Direct bilirubin greater than 1.3 times the upper limit of the normal range at visit 1.
Serum creatinine levels > 2.5 mg/dl (220 mol/l) at visit 1.
Clinically significant abnormal TSH at visit 1.
Clinically significant laboratory abnormalities, confirmed by repeat measurement, that
may interfere with the assessment of safety and/or efficacy of the study drug, other
than hyperglycemia, hyperinsulinemia, and glycosuria at visit 1.
Fasting triglycerides 700 mg/dl (>7.9 mmol/l) at visit 1.
Positive GAD antibodies at visit 1 (GAD antibodies will be tested in patients < 30
years.).
15. Evidence of significant diabetic complications, e.g., symptomatic autonomic neuropathy or gastroparesis.
16. Known sensitivity to any of the test drugs.
17. Further contraindications and warnings according to the country specific label for
pioglitazone not listed in the other exclusion criteria.
18. History of active substance abuse (including alcohol) within the past 2 years.
19. Concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study.
20. Donation of one unit (500 ml) or more of blood, significant blood loss equaling to at least one unit of blood within 2 weeks or a blood transfusion within 8 weeks prior to visit 1.
21. Potentially unreliable patients, and those judged by the investigator to be unsuitable for the study.



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

Health Condition(s) or Problem(s) studied

Diabetes mellitus

Intervention(s)

Trade Name: not extablished
Product Name: not established
Product Code: LAF 237
Pharmaceutical Form: Tablet
INN or Proposed INN: not yet established
Current Sponsor code: LAF 237
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50mg -OD
INN or Proposed INN: not established
Current Sponsor code: LAF 237
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 50mg -BID
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Actos
Product Name: Actos
Product Code: 18/270/01-C
Pharmaceutical Form: Tablet
Other descriptive name: pioglitazon
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30mg-OD
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 1 To explore the efficacy of LAF237 in patients with type 2 diabetes with HbA1c 9-11% by testing the hypothesis that the HbA1c reduction with LAF237 50 mg BID is
superior to that with pioglitazone 30 mg OD after 12 weeks of treatment.

2.To explore the efficacy of LAF237 in patients with type 2 diabetes with HbA1c 9-11% by testing the hypothesis that the responder rates (defined as reduction in HbA1c = 0,5% = 0.7% and = 1% respectively) with LAF237 50 mg BID are superior to those with LAF 237 50 OD or pioglitazone 30 mg OD after 12 weeks of treatment.

Main Objective: To demonstrate the efficacy of LAF237 in patients with type 2 diabetes with HbA1c 9-
11% by testing the hypothesis that the HbA1c reduction with LAF237 50 mg BID is
superior to that with LAF 237 50 mg OD after 12 weeks of treatment.

Primary end point(s): The primary efficacy variable is change from baseline in HbA1c at Week 12 or at the final visit with HbA1c measurement for those patients who do not have a Week 12 HbA1c measurement (the last observation carried forward (LOCF) approach). Baseline is the measurement obtained on the day of randomization (Day 1, Visit 2), or the screening measurement (Week -2, Visit 1) if Day 1 measurement is missing.

Secondary ID(s)

CLAF237A2329 / CLAF237A2329E1

Ethics review

Status: Approved
Approval date: 25/10/2004
Contact:

Results

• Results available: Yes
• Date Posted: 19/12/2016
• Date Completed: 21/06/2006
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2004-002466-38/results