| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 | | E.1.2 | Level | HLGT | | E.1.2 | Classification code | 10018424 | | E.1.2 | Term | Glucose metabolism disorders (incl diabetes mellitus) | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | The primary objective of this study is to evaluate the effect of 12-week treatment with JNJ-16269110 on the glycated hemoglobin (HbA1c) concentration in subjects with T2DM. | |
| E.2.2 | Secondary objectives of the trial | Additional obj.:
To evaluate the effect of JNJ-16269110 on:
Fasting plasma glucose
Fasting concentrations and postprandial responses of the gastrointestinal and pancreatic hormones to the standardized mixed meal
Insulin sensitivity and beta cell function based on plasma glucose, insulin and C-peptide responses to the MMTT and evaluated by HOMA2
Self-monitored blood glucose (SMBG)
Body weight, BMI and waist - hip ratio
Fasting plasma lipids including total cholesterol (TC), triglycerides (TG), VLDL, LDL, HDL and lipoproteins (ApoB 100, ApoB48 and ApoA1) and postprandial TG excursion after MMTT
BP
Safety and tolerability
Assess pharmacokinetic exposure of JNJ-16269110 to explore plasma exposure-response relationships and to develop a population pharmacokinetic model.
Evaluate QoL using Diabetes Treatment Satisfaction Questionnaires status and change (DTSQs and DTSQc) and Impact of Weight on QoL Questionnaire-Lite version (IWQOL-Lite).
Evaluate overall satisfaction
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1. Men or women with a history of T2DM and treated with a stable dose of metformin for at least 2 months prior to screening.
2. Between 18 and 70 years of age, inclusive
3. Women must be postmenopausal, defined as having a last menstrual period at least 1 year before screening with a serum follicle stimulating hormone (FSH) level consistent with postmenopausal status;
- or surgically incapable of childbearing (have had a hysterectomy or bilateral oophorectomy or tubal ligation or otherwise incapable of pregnancy);
- or if sexually active, be practicing an effective method of birth control such as hormonal contraceptives (if used consistently and correctly) including implants, injectables, transdermal patch or oral contraceptives, as well as IUDs, or
- vasectomized partner.
- sexually abstinent.
4. BMI between 25 and 45 kg/m2, inclusive, measured at screening visit.
5. HbA1c between 7% and 10%, inclusive, measured at screening visit.
6. Fasting plasma glucose not exceeding 240 mg/dL (13.3mmol/L) at baseline visit.
7. Consumption of breakfast and dinner on a daily basis.
8. Ability to swallow the intact capsule (17.5 mm in length and 9.1 mm in diameter) with water.
9. Ability and willingness to perform blood glucose monitoring using the sponsor-provided blood glucometer at home.
10. Willing to adhere to the prohibitions and restrictions specified in this protocol.
11. Subjects must have signed an informed consent document indicating tha they understand the purpose of an procedures required for the study and are willing to participate in the study.
12. To participate in the optional pharmacogenomic component of this study, subjects must have signed the informed consent for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit). Refusal to consent for this component does not exclude a subject from participation in the clinical study.
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| E.4 | Principal exclusion criteria | 1.Diabetes other than type 2 diabetes mellitus.
2.Treatment with oral anti-diabetic agents (other than metformin) or insulin during the 12 weeks before baseline visit.
3.History of intolerance or hypersensitivity to sulfonylurea or sitagliptin.
4.History of an uninterrupted period of insulin therapy for >1 month period within 1 year prior to baseline visit.
5.Active proliferative diabetic retinopathy, as defined by the application of focal or panretinal photocoagulation or vitrectomy, in the 6 months prior to baseline visit, or any other unstable (rapidly progressing) retinopathy that may require surgical treatment (including laser photocoagulation) during the study.
6.History of diabetic gastroparesis that is considered to be clinically significant in the opinion of the investigator.
7.History or evidence of liver disease, including cirrhosis, or non-alcoholic steatohepatitis/non-alcoholic fatty liver disease.
8.History of HIV or presence of hepatitis C antibodies or positive hepatitis B serology (refer to Attachment 10, Interpretation of Hepatitis B Results for Enrolling Subjects) at screening.
9.History of clinically significant gastro-intestinal disease (including but not limited to gluten and non-gluten induced enteropathy, inflammatory bowel disease, malabsorption syndromes).
10.History of hemoglobinopathy (unreliable HbA1c measurement)
11.History of major gastro-intestinal surgery other than appendectomy or uncomplicated cholecystectomy.
12.Pregnancy or nursing or women who plan to become pregnant during the study
13.History of significant cardiovascular disease, including a history of myocardial infarction (MI), unstable angina and cerebrovascular accident (CVA) within 6 months of enrollment.
14.History of clinically-significant cardiac valvular disease, significantly, congestive heart failure (cardiovascular disability functional Class III-IV according to the New York Heart Association, see Attachment 6).
15.12-lead ECG showing evidence of clinically significant heart rhythm or conduction abnormality at screening or baseline.
16.An average of 3 seated readings where diastolic blood pressure ³100 mmHg or a systolic blood pressure ³160 mmHg at screening.
17.Thyroid stimulating hormone (TSH) >1.5 X ULN at enrollment. Subjects on medication for hypothyroidism should have been on a stable dose for at least 3 months before the screening visit.
18.History of clinically significant eating disorders (anorexia nervosa, bulimia or binge eating disorder).
19.Recently (within 3 months from screening) changed smoking habits.
20.Malignancy or a history of a malignancy within 5 years before Baseline visit, other than basal cell carcinomas of the skin or in situ cervical carcinoma.
21.Increased liver function tests,
- ALT above 1.5 x ULN at screening
- any of the listed parameters: GGT, AST, total/direct bilirubin, alkaline phosphatase, LDH above 2 x ULN at screening
- if concomitant increase of two or more parameters, including
a. ALT> ULN and/or
b. AST, total/direct bilirubin, alkaline phosphatase or LDH above 1.5 X ULN and/or
c. GGT above 2x ULN at screening.
In doubtful or borderline cases, one additional retest sampling is allowed.
22.Increased creatinine kinase (CK) above ULN in subjects who take lipid lowering agents and CK level above 2 x ULN in subjects who do not take lipid lowering agents at screening visit.
23.Fasting triglycerides >6.8 mmol/L (600 mg/dL) at screening. One time repeat of the fasting triglycerides is allowed (fasting is defined as no caloric intake for at least 8 hours before the test).
24.History or evidence of clinically significant abnormal values for hematology, coagulation, or clinical biochemistry, or evidence of renal impairment (serum creatinine >133 mmol/L in men, >124 mmol/L in women).
25.History of drug or alcohol abuse within the previous 2 years prior to screening visit.
26.Alcohol consumption exceeding 4 units per day for men or 3 units per day for women; 1 unit is defined as 330 mL beer or 100 mL wine or 30 mL distilled spirits or the equivalent of this.
27.Receiving any excluded medication, refer to Section 8, Concomitant Therapy.
28.History of weight-reducing diet or receiving any drugs to treat obesity within the 3 months prior to the baseline visit
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| E.5 End points |
| E.5.1 | Primary end point(s) | | To evaluate the efficacy, safety and tolerability of JNJ-16269110 | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 60 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
