A 12-Week, Phase 2, Randomized, Double-Blind, Active-Controlled Study of LY2599506 Given as Monotherapy or in Combination with Metformin in Patients with Type 2 Diabetes Mellitus - GMAJ

• Register: EUCTR
• Last refreshed on: 26 March 2024
• Main ID: EUCTR2009-016007-39-DE
• Date of registration: 23/02/2010
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A 12-Week, Phase 2, Randomized, Double-Blind, Active-Controlled Study of LY2599506 Given as Monotherapy or in Combination with Metformin in Patients with Type 2 Diabetes Mellitus - GMAJ
• Scientific title: A 12-Week, Phase 2, Randomized, Double-Blind, Active-Controlled Study of LY2599506 Given as Monotherapy or in Combination with Metformin in Patients with Type 2 Diabetes Mellitus - GMAJ
• Date of first enrolment: 27/05/2010
• Target sample size: 193
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016007-39
• 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: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Czech Republic, Germany, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
[1] Have type 2 diabetes mellitus prior to entering the trial based on the disease diagnostic criteria (WHO) classification.
[2] Are currently being treated with diet and exercise therapy consistent with the local standards of medical care, in the opinion of the Investigator.
[3] Patients may be treated with:
Diet and exercise alone OR Diet and exercise in combination with a stable dose of metformin for at least 3 months before Visit 1 OR Diet and exercise in combination with a stable dose of sulfonylurea for at least 3 months before Visit 1 OR Diet and exercise in combination with stable doses of metformin and sulfonylurea for at least 3 months before Visit 1 and have had diabetes for at least 6 years.
[4] Have an HbA1c value between 7% and 10%, inclusive at Visit 1.
[5] Are men or women between the ages of 18 to 70 years, inclusive.
[6] Are women not of child-bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Male patients will be advised to use a reliable method of birth control during the study and until 3 months after the last dose of study medication if their partner is of child-bearing potential. These requirements do not apply if the patient or his partner has been surgically sterilized.
[7] Have a body mass index between 20 and 40 kg/m2, inclusive at Visit 1.
[8] Have stable weight during the 3 months prior to Visit 1 (weight change not to exceed 5 kg over this period by patient self-report).
[9] Are well motivated, capable, and willing to (in the opinion of the Investigator):
• perform SMBG;
• complete study diary/ies, as required for this protocol;
• be receptive to diabetes education, including continuing their prestudy diet and activity levels, and follow simple dietary advice as appropriate.
[10] Have given written informed consent to participate in this study in accordance with local regulations and the ERB governing the study site.

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:
[11] Use of insulin or any antidiabetic agent other than metformin or sulfonylurea during the 3 months prior to Visit 1.
[12] Have a gastrointestinal disease that significantly impacts gastric empting or motility (for example, severe gastroparesis or pyloric stenosis) , in the opinion of the Investigator, or have undergone gastric bypass or gastric banding surgery.
[13] Have had more than 1 episode of severe hypoglycemia within 6 months prior to entry into the study, or are currently diagnosed as having hypoglycemia unawareness.
[14] Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months.
[15] Are currently taking or have taken within the last 2 months medications which affect body weight.
[16] Have cardiac autonomic neuropathy (for example, resting tachycardia or orthostatic hypotension), based on clinical signs, symptoms, or appropriate diagnostic testing.
17] Have cardiac disease with functional status that is NYHA Class II, III, or IV or a history of myocardial infarction, unstable angina, or decompensated congestive heart failure in the past 6 months.
[18] Have poorly controlled hypertension (that is, mean systolic blood pressure >160 mm/Hg or mean diastolic blood pressure >100 mm/Hg) confirmed by 2 separate blood pressure measurements at Visit 1, history of malignant hypertension, evidence of renal artery stenosis and/or evidence of labile blood pressure including symptomatic postural hypotension. Doses of antihypertensive medications must be stable for 30 days before randomization.
[19] Have a QTcB (Bazett’s-corrected QT interval) interval greater than 450 msec for men or greater than 470 for women at Visit 1 or any personal history of ventricular tachycardia or unexplained syncope.
[20] Have family history of long QT syndrome or family history of sudden death.
[21] Use prescriptions or over-the-counter medications known to prolong the QT interval.
[22] Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or repeated alanine transaminase (ALT) levels >2.5 times the upper limit of the reference range at Visit 1, as determined by the central laboratory. (Patients with alanine aminotransferase [ALT] >2 times the upper limit of normal [ULN] should be evaluated for hepatitis).
[23] Have a serum creatinine >2.0 mg/dL (177 µmol/L) or in patients being treated with metformin, a serum creatinine above (or creatinine clearance below) what is approved in the metformin product labeling in the respective country, or are currently receiving renal dialysis.
[24] Have fed or fasting state hypertriglyceridemia (defined as >6.8 mmol/L, 600 mg/dl) at Visit 1. If taking lipid-lowering agents, doses of these medications must be stable for 30 days prior to randomization.
[25] Have evidence of inadequately treated hypothyroidism or hyperthyroidism based on clinical evaluation and/or an abnormal TSH result and which would confound data interpretation or pose a risk to patient safety. Subjects on a stable dose of thyroid replacement therapy may be eligible if they meet the other criteria.
[26] Have a history of a transplanted organ (except for corneal keratoplasty).
[27] Have evidence of a significant active, uncontrolled endocrine or autoimmune abnormality.
[28] Are receiving chronic (>2 weeks) systemic glucocorticoid therapy (excluding topical or inhaled preparations) or have received such therapy within 4 weeks immediately prior to Visit 2.
[29] Have an activ

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

Health Condition(s) or Problem(s) studied

Type 2 diabetes
MedDRA version: 9.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus

Intervention(s)

Product Name: Glucokinase activator 1
Product Code: LY2599506
Pharmaceutical Form: Capsule, hard
CAS Number: 745051-65-4
Current Sponsor code: LY2599506
Other descriptive name: Glucokinase activator 1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50 -
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Glibenclamide
Product Name: glibenclamide
Pharmaceutical Form: Tablet
INN or Proposed INN: GLIBENCLAMIDE
CAS Number: 10238218
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Glucokinase activator 1
Product Code: LY2599506
Pharmaceutical Form: Capsule, hard
CAS Number: 745051-65-4
Current Sponsor code: LY2599506
Other descriptive name: Glucokinase activator 1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this study is to test the hypothesis that, for adult patients with T2DM treated with or without metformin, administration of LY2599506 significantly decreases the HbA1c from baseline to endpoint at 12 weeks as compared to glyburide.

Secondary Objective: • To evaluate the safety and tolerability of LY2599506 in patients with T2DM.
• To evaluate the effects of LY2599506 and glyburide on frequency and severity of hypoglycemia.
• To evaluate the effects of LY2599506 and glyburide on fasting and post-prandial glucose.
• To evaluate the effects of LY2599506 and glyburide on insulin sensitivity, glucose clearance, and ß-cell function.
• To evaluate the popPK and pharmacodynamics of LY2599506 on HbA1c, fasting glucose, fasting insulin, OGTT, glucose AUC, and OGTT insulin AUC endpoints.
• To evaluate the effects of LY2599506 and glyburide on fasting lipids and lipoproteins.
• To evaluate the frequency, extent of dose adjustment, and distribution of doses during 12 weeks of treatment for LY2599506 and glyburide.
• To evaluate the effects of LY2599506 and glyburide on patient-reported outcomes
• To evaluate the effects of LY2599506 and glyburide on change in body weight from baseline to endpoint.

Primary end point(s): The mean change in HbA1c from baseline to endpoint is the primary efficacy measure.

Secondary ID(s)

2009-016007-39-CZ

I2Q-MC-GMAJ

Ethics review

Status: Approved
Approval date: 21/04/2010
Contact:

Results

• Results available: Yes
• Date Posted: 18/01/2018
• Date Completed: 03/06/2010
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-016007-39/results