| 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] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045242 |
| E.1.2 | Term | Type II diabetes mellitus |
| E.1.2 | System Organ Class | 100000004861 |
|
| 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 |
Base and extension study
Over 20 weeks (base) and over 54 weeks (extension)-assess safety and
tolerability of the addition of sitagliptin (as MK-0431A) in pediatric
patients (10-17 y.) with T2DM with inadequate glycemic control on
metformin therapy
Base study
Pooled population ( MK-0431A P170 base study and MK-0431A XR P289
Phase A) to assess in pediatric patients (10-17 y.) with T2DM with
inadequate glycemic control on metformin therapy
1 After 20 weeks effect of the addition of sitagliptin (as MK-0431A or
MK-0431A XR) relative to placebo on A1C
2 Over 20 weeks safety and tolerability of the addition of sitagliptin (as
MK-0431A or MK-0431A XR)
Extension study
Pooled population [MK-0431A P170(base+extension study) and MK-
0431A XR P289(Phase A+B)]
Over 54 weeks to assess the safety and tolerability of the addition of
sitagliptin (as MK-0431A or MK-0431A XR) in pediatric patients (10-17
y.) with T2DM with inadequate glycemic control on metformin
therapy |
|
| E.2.2 | Secondary objectives of the trial |
Base study
Pooled population (MK-0431A P170 base study and MK-0431A XR P289
Phase A) - to assess after 20 weeks the effect of the addition of
sitagliptin (as MK-0431A or MK-0431A XR) on:
1 fasting plasma glucose (FPG);
2 proportion of patients initiating glycemic rescue therapy;
3 proportion of patients with A1C at goal (<7.0%)
- all relative to placebo in pediatric patients (10-17 y.) with T2DM with
inadequate glycemic control on metformin therapy:
Extension study
Pooled population [MK-0431A P170(base+extension study) and MK-
0431A XR P289(Phase A+B)] - to assess after 54 weeks the effect of the
addition of sitagliptin (as MK 0431A or MK-0431A XR) on:
1 changes from baseline in A1C
2 changes from baseline in FPG
3 proportion of patients with A1C at goal (<7.0%)
- in pediatric patients (10-17 y.) with T2DM with inadequate glycemic
control on metformin therapy |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Base study:
1. Patient has type 2 diabetes mellitus (T2DM).
3. Patient on metformin monotherapy (≥1500 mg/day, for ≥12 weeks) with A1C ≥6.5%
and ≤10.0%
OR
Patients is on stable doses of metformin (≥1500 mg/day, for ≥12 weeks) and insulin
(of any type, variance in dose to be ≤15% of total daily dose for ≥12 weeks prior to
Screening Visit/ Visit 1) with an A1C≥7.0% and 10%.
i. Patients on stable doses of metformin ≥1000 and <1500 mg/day (± insulin) for
≥12 weeks can participate if there is documentation that they cannot tolerate
higher doses of metformin.
ii. Patients on metformin doses <1500 mg/day (± insulin) can have their metformin
doses uptitrated to ≥1500 mg/day, and be eligible to participate after their dose
remains stable for ≥12 weeks, if they meet all other eligibility criteria.
iii. At screening, patients on insulin doses that are not stable can have the insulin
doses adjusted and be eligible to participate after their dose remains stable for ≥12
weeks, if they meet all other eligibility criteria.iv. Patients currently being treated with an AHA (other than insulin) in addition to
metformin cannot be included in the study after wash-off.
4. Patient is ≥10 and ≤17 years of age on day of signing informed
consent with randomization to occur prior to the patient's 18th birthday.
5. Patient is either a male, or patient is a female who is unlikely to
conceive as indicated by at least one "yes" response to the following
which will remain consistent for the projected duration of the study and
for 14 days after the last dose of study medication: (a) Patient is a nonsterilized
female who is currently not sexually active and agrees to
follow statement "c" if heterosexual activity is initiated or (b) Patient
agrees to abstain from heterosexual activity or (c) Patient agrees to use
an adequate method of contraception.
For complete list of inclusion crtieria please refer to the protocol
Extension study:
1. Patient has completed the P170 base study on double-blind study
medication.
2. Parent/guardian understands the study procedures and risks involved
with the study and voluntarily agrees to the patient's participation by
giving informed written consent, and the patient has an age-appropriate
understanding of the same to give informed written assent. If the parent/guardian is illiterate, please see Section 3.2.3.8.1 for details.
Note: Patients, who are legally able to, should provide consent.
3. Patient and/or a family member or adult closely involved in the
patient's daily activities (in the opinion of the investigator) will be
available for telephone calls and study visits.
4. Patient is either a male, or patient is a female who is unlikely to
conceive as indicated by at least one "yes" response to the following
which will remain consistent for the projected duration of the study and
for 14 days after the last dose of study medication: (a) Patient is a
nonsterilized female who is currently not sexually active and agrees to
follow statement "c" if heterosexual activity is initiated or (b) Patient
agrees to abstain from heterosexual activity or (c) Patient agrees to use
an adequate method of contraception. |
|
| E.4 | Principal exclusion criteria |
Base study:
At Visit 1
1. Patient has (1) known type 1 diabetes mellitus or documented
evidence of positive diabetes auto-antibodies (if performed when patient
was diagnosed with diabetes), or (2) known monogenic diabetes,
secondary diabetes, or a genetic syndrome or disorder known to affect
glucose tolerance other than diabetes.
2. Patient has symptomatic hyperglycemia and/or moderate to large
ketonuria or positive test for ketonemia requiring immediate initiation of
another antihyperglycemic agent.
3. Patient has previously taken a DPP-4 inhibitor (such as sitagliptin,
vildagliptin, alogliptin, or saxagliptin) or GLP-1 receptor agonist (such as
exenatide or liraglutide.
For complete list of exclusion criteria please refer to the protocol
Extension study:
1. Patient meets a discontinuation criterion of P170 at the last visit of
the base study (Week 20).
2. Patient has taken the last dose of study medication for the P170 base
study more than 14 days prior to Extension Visit 1.
3. Patient has initiated another oral antihyperglycemic agent (ie, other than study drug
or metformin).
4. Patient does not agree to refrain from participating in any other
double-blind interventional study while participating in this extension
study.
5. Patient is unlikely to adhere to the study procedures and appointment
schedule, has poor mental function or parent/guardian is, in the opinion
of the investigator, mentally or legally incapacitated preventing informed
consent from being obtained.
6. Patient has a history or current evidence of any condition, therapy, lab
abnormality or other circumstance which, in the opinion of the
investigator, might pose a risk to the patient, or make participation not
in the patient's best interest. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Base study:
change from baseline in hemoglobin A1c (A1C)
Extension study:
Change from baseline in A1C at Week 54
Proportion of patients meeting A1C goal <7.0% and <6.5% at Week 54
Change from baseline in FPG at Week 54
Proportion of patients initiating insulin glargine in P170 extension study
Percent change from baseline in lipid panel at Week 54
-Triglycerides (TG)
- LDL-C
- HDL-C
- non-HDL-C
- Total cholesterol (TC) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Base study - Week 20
Extension study - week 54 |
|
| E.5.2 | Secondary end point(s) |
Base study:
Change from baseline in FPG
Percentage of patients with A1C at goal (<7.0% as primary; <6.5% as
secondary) at Week 20
Percentage of patients initiating glycemic rescue therapy |
|
| 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 | Yes |
| 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 | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | No |
| 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 | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 22 |
| 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 |
| Argentina |
| Australia |
| Austria |
| Belarus |
| Belgium |
| Brazil |
| Bulgaria |
| Canada |
| Chile |
| China |
| Colombia |
| Costa Rica |
| Croatia |
| Czech Republic |
| Denmark |
| Dominican Republic |
| Ecuador |
| Estonia |
| France |
| Georgia |
| Germany |
| Greece |
| Guatemala |
| Hungary |
| India |
| Indonesia |
| Ireland |
| Israel |
| Italy |
| Korea, Republic of |
| Latvia |
| Lithuania |
| Malaysia |
| Mexico |
| Netherlands |
| New Zealand |
| Norway |
| Panama |
| Peru |
| Philippines |
| Poland |
| Portugal |
| Puerto Rico |
| Romania |
| Russian Federation |
| Saudi Arabia |
| Serbia |
| Singapore |
| Slovenia |
| South Africa |
| Spain |
| Sri Lanka |
| Taiwan |
| Thailand |
| Tunisia |
| Turkey |
| Ukraine |
| United Arab Emirates |
| United Kingdom |
| United States |
| Vietnam |
| Venezuela, Bolivarian Republic of |
|
| 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 | 5 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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