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

• Register: EUCTR
• Last refreshed on: 28 April 2014
• Main ID: EUCTR2011-002931-25-CZ
• Date of registration: 30/01/2012
• 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: 19/04/2012
• 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

Belarus, Czech Republic, Hungary, Israel, Mexico, Poland, Romania, 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 or TZDs (eg, rosiglitazone or pioglitazone) for at least 24 weeks prior to Screening

5. Body mass index (BMI) 25kg/m2 to 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). A onetime central laboratory re-test of FSG is allowed in subjects with an initial central laboratory FSG =125 mg/dL (6.9 mmol/L) and <130 mg/dL (7.2 mmol/L) who are otherwise eligible as determinedby the Investigator.

8. Fasting serum C-peptide = 0,8 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 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 or current diagnosis of Type 1 Diabetes Mellitus
2. History of diabetic ketoacidosis, ketosis-prone diabetes, or hyperosmolar hyperglycemic coma
3. History of a severe episode of hypoglycemia (=1 episode within 3 months prior to Screening or =2 episodes within 6 months prior to Screen.), defined as hypoglycemia requiring 3rd party assistance to actively administer carbohydrate, glucagon, or other
resuscitative actions due to severe impairment in consciousness or behavior
4. Clin. signif.complications of diabetes that, in the judgment of the investigator, would make subjects unsuitable to participate in this study
- Medical Exclusions:
5. History of any clin. signifi. cardiovascular or cerebrovascular
event = 3 months prior to Screen.
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. HistHistory of bariatric surgery at any time in the past or any other
surgery <2 months before Screen.; or planning to undergo surgery during the study. Subjects with a planned minor surgery may be enrolled upon approval by the Medical Monitor.
9. Any other hospitalization in the 14 days prior to Screen. or planned hospitalization at any time during the study.

10. Significant weight change (± 5%) < 2 months prior to Screen. or on a weight-loss program and is not in the maintenance phase at Screen.

11. Severe renal impairment, defined as an estimated glomerular
filtration rate (eGFR) by the Modification of Diet in Renal Disease
(MDRD) equation < 30 mL/min/1.73 m2 at Screening or 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 (Child-Pugh Class A, B, or C).
13. Active liver disease and/or significant abnormal liver function
defined as AST> 3x ULN and/or ALT> 3x ULN and/or serum total bilirubin > 2.0 mg/dL
14. History of cancer (except non-melanomic skin cancers or cervical in situ) within 5 years prior to Screening.
15. History of alcohol or other drug abuse < 12 months prior to Screening
16. Any other clin. signif. existing medical or psychiatric condition, inc. clin. signif. lab. 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:
17. Prior treatment with open-label ranolazine or known hypersensitivity or intolerance to ranolazine
18. Treatment with strong or moderate CYP3A inhibitors or P-gp
inhibitors within 14 days prior to Random.
19. Treatment with CYP3A inducers or P-gp inducers within 14 days prior to Random.
20. Treatment with CYP3A4 substrates with a narrow therapeutic range within 14 days prior to Random.
21. Treatment with simvastatin at a daily dose of > 20 mg or lovastatin
at a daily dose > 40 mg, within 14 days prior to Random.
22. Weight-loss medication or anti-obesity m

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

Health Condition(s) or Problem(s) studied

Type 2 Diabetes Mellitus
MedDRA version: 16.0 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)

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 (or TZDs in the 24
weeks) prior to Screening

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

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 (or TZDs in the 24
weeks) prior to Screening

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

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoints of this study are:
• Change from Baseline in incremental change of 2-hour PPG at Week 24
• Change from Baseline in FSG at Week 24 or change from Baseline in 2-hour PPG at Week 24

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

Secondary ID(s)

GS-US-259-0131

2011-002931-25-HU

Source(s) of Monetary Support

Gilead Sciences, Inc.