| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10067585 |
| E.1.2 | Term | Type 2 diabetes mellitus |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
| 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 |
(1) After 24 weeks, to assess the effect of treatment with MK-3102
compared with placebo on A1C.
(2) To assess the safety and tolerability of MK-3102.
|
|
| E.2.2 | Secondary objectives of the trial |
1) After 24 weeks, to assess the effect of MK-3102 compared with
placebo on fasting plasma glucose (FPG).
(2) After 24 and 54 weeks, to assess the effect (change from baseline)
of MK-3102 on eGFR.
(3) After 54 weeks, to assess |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
At Visit 1
- Have T2DM and be ≥30 years of age on day of signing informed
consent. Note: For India only: Subject has T2DM and is ≥30 and ≤65
years of age on day of signing informed consent.
- Have moderate or severe chronic renal insufficiency as indicated by an
eGFR <60 mL/min/1.73 m2. Note: Glomerular filtration rate is
estimated using the Modification of Diet in Renal Disease (MDRD)
formula (see Section 12.5); OR, Subject is on dialysis (hemodialysis or
peritoneal dialysis) for at least 6 months on the day of signing informed
consent.
- Meet one of the following criteria as indicated by a "yes" answer: a)
Subject is currently not on an AHA (off therapy for ≥12 weeks) and has a
Visit 1 A1C ≥7.0% (53 mmol/mol) and ≤10.0% (86 mmol/mol); OR b)
Subject is currently on a single oral AHA or low-dose dual oral combination AHA (i.e., at ≤50% of maximum labeled dose of each agent)
and has a Visit 1 A1C of ≥6.5% (48 mmol/mol) and ≤9.0% (75
mmol/mol); OR c) Subject is currently on a stable insulin regimen, at a
dose of at least 15 U/day, for ≥10 weeks, with no oral AHA, and has a
Visit 1 A1C ≥7.5% (58 mmol/mol) and ≤10.0% (86 mmol/mol) and FPG
>130 mg/dL (7.22 mmol/L). Subjects may be receiving pre-mixed (e.g.,
Novolog 70/30®, Novolin 70/30®, Humalog 75/25®, or Humulin
70/30®), intermediate-acting (e.g., NPH), or long-acting (e.g., glargine,
detemir, degludec) insulin therapy. Pre-meal short-acting (e.g., regular insulin) or rapid- acting (e.g., lispro aspart, glulisine) insulins are not allowed. Note: a stable insulin regimen is defined as all daily doses within 10% of a usual administered daily dose (i.e., if usual daily dose is 50 U/day, doses 45-55 U/day would be considered as stable).
- Meets one of the following criteria:
a. Subject is a male;
b. Subject is a female not of reproductive potential defined as one who
has either:
(1) reached natural menopause (defined as ≥12 months of spontaneous amenorrhea in women >45 years of age, or ≥6 months of spontaneous amenorrhea with serum follicular stimulating hormone [FSH] levels in the postmenopausal range as determined by the laboratory), or
(2) had a hysterectomy and/or bilateral oophorectomy, or had bilateral tubal ligation or occlusion at least 6 weeks prior to screening. c. Subject is a female of reproductive potential and:
(1) agrees to remain abstinent from heterosexual activity (if this form of birth control is accepted by local regulatory agencies and ethics review committees as the sole method of birth control), or
(2) agrees to use (or have their partner use) acceptable contraception to prevent pregnancy within the projected duration of the trial and for 28 days after the last dose of blinded study medication. Two methods of contraception will be used to avoid pregnancy. Acceptable combinations of methods include:
- Use of one of the following double-barrier methods: diaphragm with spermicide and a condom; cervical cap and a condom; or contraceptive sponge and a condom.
- Use of hormonal contraception (any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent [including oral, subcutaneous, intrauterine and intramuscular agents, and cutaneous patch]) with one of the following: diaphragm with spermicide; cervical cap; contraceptive sponge; condom; vasectomy; or intrauterine device (IUD).
- Use of an IUD with one of the following: condom; diaphragm with spermicide; contraceptive sponge; vasectomy; or hormonal contraception (see above).
- Vasectomy with one of the following: diaphragm with spermicide; cervical cap; contraceptive sponge; condom; IUD; or hormonal contraception (see above).
- Understand the trial procedures, alternative treatments available, and risks involved with the trial and voluntarily agrees to participate by giving written informed consent. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
At Visit 3/Week -2
- Have an eGFR (using MDRD formula) <60 mL/min/1.73 m2.
- Meet one of the following criteria measured at or within 2 weeks prior to Visit 3/Week -2 as indicated by a "yes" answer:
a) Subject not on an AHA or "washed-off" from AHA therapy has A1C ≥ 7.0% (53 mmol/mol) and ≤10.0% (86 mmol/mol).
b) Subject on insulin monotherapy at screening has A1C ≥7.5% (58mmol/mol) and ≤10.0% (86 mmol/mol) and FPG >130 mg/dL (7.22 mmol/L). Note: Once a subject has initiated placebo run-in at Visit 3/Week -2, if
the Visit 3 A1C is not within the Visit 3 A1C inclusion criterion, a single
repeat measurement may be performed at the discretion of the investigator. If the repeat value meets Visit 3 A1C inclusion criterion, the subject may continue in the trial. At Visit 4/Day 1 Randomization
- Must be 100% compliant with MK-3102 matching placebo study medication during the single-blind placebo run-in (as determined by site-performed capsule count). |
|
| E.4 | Principal exclusion criteria |
- Has a history of T1DM or a history of ketoacidosis, OR is assessed as
possibly having T1DM confirmed with a C-peptide <0.7 ng/mL (0.23
nmol/L).
- Has been treated with any incretin mimetic or TZD within the prior 12
weeks of Visit 1/screeningor with MK-3102 at any time prior to signing
informed consent.
- Has a history of hypersensitivity to a DPP-4 inhibitor.
- Is currently participating, or has participated, in a trial in which the
subject received an investigational compound or used an investigational
device within the prior 12 weeks of signing ICF
- Has a history of intolerance or hypersensitivity or other
contraindication to glipizide (ONLY for subjects who are not on
background therapy with insulin). Note: Subjects with severe chronic
renal insufficiency or ESRD are allowed to take glipizide in this trial,
except if prohibited by the local regulatory authority or ethics committee
overseeing the investigational site. OR Has a history of intolerance or
hypersensitivity to insulin glargine or any contraindication to insulin
glargine based upon the label in the country of the investigational site.
- Is on a weight loss program and is not in the maintenance phase, or
has been on a weight loss medication in the past 6 months or has
undergone bariatric surgery within 12months prior to signing the ICF.
- Has undergone a surgical procedure within 4weeks prior to signing ICF
or has planned major surgery during the trial.
- Is on or likely to require treatment for ≥14 consecutive days or
repeated courses of pharmacologic doses of corticosteroids.
- Is currently being treated for hyperthyroidism or is on thyroid
replacement therapy and has not been on a stable dose for at least 6
weeks.
- Is currently on or likely to require treatment with a prohibited
medication
- If subject is on dialysis and does not regularly adhere to dialysis schedule.
- Has a diagnosis of CHF with NYHA Class IV
- Has a medical history of active liver disease or symptomatic gallbladder disease.
- Has HIV as assessed by medical history.
- Has had new or worsening signs or symptoms of CHD or CHF within the past 3 months
- Has poorly controlled hypertension.
- Has severe active peripheral vascular disease
- Has a history of malignancy ≤5 years prior to signing informed consent,
except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
- Has a clinically significant hematological disorder
- Has exclusionary laboratory values as listed in the protocol
- Has a positive pregnancy test.
- Is pregnant or breast-feeding, or is expecting to conceive during the trial, including 28 days following the last dose of blinded study medication, OR Is expecting to undergo hormonal therapy in preparation to donate eggs during the period of the trial, including 28 days following the last dose of blinded study medication.
- Is, at the time of signing informed consent, a user of recreational or
illicit drugs or has had a recent history of drug abuse OR subject routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking.
- Has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that makes participation not in the subject's best interest, might interfere with the subject's participation for the full duration of the trial, or might confound the results of the trial.
- Is unlikely to adhere to the trial procedures, keep appointments, or is
planning to relocate during the trial.
- Has a FPG consistently >260 mg/dL (14.43 mmol/L) and is not considered likely to improve glycemic control with diet and exercise counseling.
- Has a clinically significant ECG abnormality
- Has a FPG consistently >260 mg/dL (14.43 mmol/L).
- Has symptomatic hyperglycemia that, in the investigator's opinion,
requires immediate initiation, adjustment, or addition of antihyperglycemic therapy.
- Has poorly controlled hypertension defined as a systolic blood pressure of ≥160 mmHg or diastolic blood pressure of ≥90 mmHg.
- Is on lipid-lowering medication or thyroid replacement therapy, and
has not been on a stable regimen for the 4 weeks (lipid-lowering medication) or 6 weeks (thyroid replacement therapy) prior to Visit 4/Day 1.
- Has a positive pregnancy test at Visit 4/Day 1
- Has a site FFSG of <130 mg/dL (7.22 mmol/L) or >260 mg/dL (14.43
mmol/L).
- Has symptomatic hyperglycemia that, in the investigator's opinion, requires immediate initiation, adjustment, or addition of antihyperglycemic therapy.
- Has developed a new medical condition, suffered a change in status of an established medical condition, developed a laboratory abnormality or ECG abnormality, or required a new treatment or medication during the pre-randomization period which meets any previously described trial exclusion criteria or which, in the opinion of the investigator, exposes the subject to risk by enrolling in the trial. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| - Change from baseline in A1C at Week 24 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Change from baseline in A1C at Week 54
- Change from baseline in FPG at Week 24/Week 54 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 14 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Croatia |
| European Union |
| Hong Kong |
| India |
| Israel |
| Malaysia |
| Philippines |
| Russian Federation |
| Serbia |
| Turkey |
| United States |
|
| 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 | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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