A study to investigate a new drug to treat Type 2 Diabetes

• Register: EUCTR
• Last refreshed on: 14 March 2016
• Main ID: EUCTR2011-002931-25-SK
• Date of registration: 12/04/2012
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: A study to investigate a new drug to treat Type 2 Diabetes
• Scientific title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Ranolazine Monotherapy in Subjects with Type 2 Diabetes Mellitus
• Date of first enrolment: 30/04/2012
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002931-25
• 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: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Czech Republic, Hungary, Poland, Russian Federation, Serbia, Slovakia, South Africa, Ukraine, United States

Contacts

• Name: International Regulatory Affairs
• Affiliation: Gilead Sciences International Ltd

• Name: International Regulatory Affairs
• Affiliation: Gilead Sciences International Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
1. Written informed consent

2. Males and females, 18 to 75 years old, inclusive

3. Documented history of T2DM

4. Treatment naïve to antihyperglycemic therapy or having received no prior treatment with antihyperglycemic therapy for at least 90 days prior to Screening

5. Body mass index (BMI) 27-45 kg/m2 inclusive at Screening

6. HbA1c 7% - 10% inclusive, at Screening and at the end of Qualifying Period (Day 14 +2 days)

7. FSG of = 130 mg/dL (7.2 mmol/L) and = 240 mg/dL (13.3 mmol/L) at Screening and at the end of Qualifying Period (Day 14 +2 days)

8. C-peptide > 1.0 ng/mL at Screening

9. Ability and willingness to comply with all study procedures during the course of the study

10. Females of child-bearing potential must have a negative pregnancy test at Screening (unless surgically sterile or > 2 years post-menopausal) and must agree to use highly effective contraception methods from Screening throughout the duration of the Treatment Period and for 14 days following the last dose of study drug

11. At least 80% compliant with dosing during the Qualifying Period

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 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion criteria:
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:

- Diabetes- Specific Exclusions:
1. History of Type 1 Diabetes Mellitus

2. History of acute or chronic ketoacidosis, ketosis-prone diabetes, or hyperosmolar hyperglycemic coma

3. History of a severe episode of hypoglycemia (eg, requiring assistance of another person or active intervention of any kind) < 3 months before Screening

4. Clinically significant complications of diabetes that, in the judgment of the investigator, would make subjects unsuitable to participate in this study

- Medical Exclusions:
5. Any clinically significant cardiovascular or cerebrovascular event = 3 months prior to Screening

6. Inadequately controlled or unstable hypertension as defined by systolic blood pressure (SBP) > 160 mmHg or diastolic blood pressure (DBP) > 100 mmHg at Screening and Randomization.

7. Prolonged QTc interval > 500 msec by ECG at Screening, a personal or family history of QTc prolongation, congenital long QT syndrome, or subjects who are receiving drugs that prolong the QTc interval, such as Class Ia or Class III antiarrhythmic agents, erythromycin, and certain antipsychotics (eg, ziprasidone)

8. History of bariatric surgery at any time in the past or any other surgery < 2 months before Screening, or any planned surgery, that, in the opinion of the investigator, might have an effect on glucose homeostasis

9. Any other hospitalization in the 14 days prior to Screening or planned hospitalization at any time during the study.

10. Significant weight change (± 5%) < 2 months prior to Screening

11. Undergoing any type of dialysis at Screening or planning to undergo any type of dialysis at any time during the course of the study

12. History of liver cirrhosis

13. History of substance abuse < 12 months prior to Screening

14. Excessive alcohol consumption that, in the opinion of the investigator, would likely affect the subject’s glucose homeostasis

15. Any other clinically significant existing medical or psychiatric condition, including clinically significant laboratory abnormalities, or one requiring further evaluation that, in the opinion of the investigator, could interfere with conduct of the study or interpretation of the data

- Medications Exclusions:
16. Prior treatment with open-label ranolazine or known hypersensitivity or intolerance to ranolazine

17. Treatment with strong or moderate CYP3A inhibitors within 14 days prior to Randomization

18. Treatment with CYP3A inducers or P-gp inducers within 14 days prior to Randomization

19. Treatment with CYP3A4 substrates with a narrow therapeutic range within 14 days prior to Randomization

20. Treatment with simvastatin at a daily dose of > 20 mg within 14 days prior to Randomization

21. Treatment with a thiazolidinedione (TZD) (eg, rosiglitazone or pioglitazone) within 6 months of Screening.

22. Weight-loss medication or anti-obesity medication (prescription or non-prescription) < 3 months prior to Screening

23. Treatment with niacin > 200 mg daily; if receiving = 200 mg daily, should be on stable doses for = 90 days prior to Screening and for the duration of the study

24. Expected or current treatment with systemic corticosteroids (oral or injectable) for a > 14 days from Screening through the end of the Treatment Period. Topical or inhaled corticosteroid formulations are permitted at any time during the study

25. If rec

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

Health Condition(s) or Problem(s) studied

Type 2 Diabetes Mellitus
MedDRA version: 14.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Trade Name: Ranexa®
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: RANOLAZINE
CAS Number: 95635-55-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint of this study is:
• Change from Baseline in HbA1c at Week 24

Timepoint(s) of evaluation of this end point: Week 24

Main Objective: The primary objective of this study is to:
• Determine the effect of ranolazine monotherapy on HbA1c in subjects with T2DM who are inadequately controlled with diet and exercise alone and who are treatment naïve to
antihyperglycemic therapy or have not received antihyperglycemic therapy in the 90 days prior to Screening

Secondary Objective: The secondary objectives of the study are to:
• Determine the effect of ranolazine monotherapy on postprandial glucose (PPG)
• Determine the effect of ranolazine monotherapy on fasting serum glucose (FSG)

The additional objectives of the study are to:
• Evaluate the effect of ranolazine monotherapy on each of the following endpoints: serum C-peptide, serum insulin, plasma glucagon
• Evaluate the pharmacokinetics (PK) of ranolazine
The safety objective of the study is to:
• Evaluate the safety and tolerability of ranolazine monotherapy in subjects who are treatment naïve to antihyperglycemic therapy or have not received antihyperglycemic therapy in the 90 days prior to Screening

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoints of this study are:
• Change from Baseline in postprandial serum glucose through Week 24
• Change from Baseline in fasting serum glucose through Week 24

Timepoint(s) of evaluation of this end point: Week 24

Secondary ID(s)

2011-002931-25-HU

GS-US-259-0131

Source(s) of Monetary Support

Gilead Sciences, Inc.