E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 16.0 |
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 |
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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 |
To address in type 2 diabetic patients compared to baseline the effect of repeated doses of Lyxumia® and Lantus® after an eight weeks two-step treatment regimen (four weeks administration of either
Lyxumia® or Lantus®, both followed by their combined administration for another four weeks) on
- intravenous glucose tolerance test (IVGTT) related first phase insulin secretion |
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E.2.2 | Secondary objectives of the trial |
To address in type 2 diabetes patients compared to baseline the effect
1. of repeated doses of Lyxumia® and Lantus® after an eight weeks two step treatment regimen
(four weeks administration of either Lyxumia® or Lantus®, followed by combined administration
for another four weeks)
2. of treatment sequence (four weeks administration of Lyxumia® vs. four weeks administration of
Lantus®, both followed by a combined administration for another four weeks)
glucagon, as well as serum levels of free fatty acids, TGs, and on gastric emptying
To assess Lyxumia® safety and tolerability as add on treatment to Lantus® and metformin |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects, between 18 and 75 years of age, inclusive.
2. Body mass index between 20.0 and 40.0 kg/m2, inclusive.
3. Male or female subjects with type 2 diabetes mellitus for at least 1 year at the time of
the screening visit, not adequately controlled under therapy with metformin or
metformin plus sulfonylurea, DPPIV inhibitor and dapagliflozin (FPG > 7.8 mmol·L-1,
HbA1c (glycosylated hemoglobin) ≥7.0% and HbA1c ≤9.5% at screening)
4. If female, subject must use a double contraception method, except if she has
undergone sterilization at least 3 months earlier or is postmenopausal. The accepted
double contraception methods include use of a highly effective method of birth control
(intrauterine device or hormonal contraception) in addition to one of the following
contraceptive options: (1) condom; (2) diaphragm or cervical/vault cap; (3)
spermicide.
5. Having given written informed consent prior to undertaking any study-related
procedure.
6. Covered by a health insurance system where applicable, and/or in compliance with
the recommendations of the national laws in force relating to biomedical research.
Not under any administrative or legal supervision. |
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E.4 | Principal exclusion criteria |
1. Subjects with type 1 diabetes, maturity onset diabetes of the young (MODY) or
secondary forms of diabetes such as due to pancreatitis
2. Current or previous treatment with insulin (except for treatment within a clinical trial,
for surgical procedures or during an acute illness for ≤ 7 days and more than 14 days
before the first administration of study drug)
3. Treatment with any hypoglycaemic medication other than metformin or metformin
combined with sulfonylurea, DPPIV inhibitor or dapagliflozin within the three months
prior to screening. Exception: treatment with a glitazone for 4 weeks and more than
three months prior to screening.
4. FPG 13.9 mmol·L-1 at screening or before randomisation (V2) |
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E.5 End points |
E.5.1 | Primary end point(s) |
AUCISEC(0-10min) First phase insulin secretion – area under the insulin secretion rate-time curve
within 0 to 10 min after iv glucose challenge |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Key secondary endpoints (IVGTT-related)
AUCISEC(10-120min) Second phase insulin secretion – area under the insulin secretion rate-time
curve within 10 to 120 min after iv glucose challenge
AUCC-PEP(0-10min) Area under the C-peptide concentration-time curve within 0 to 10 min after iv
glucose challenge
AUCC-PEP(10-120min) Area under the C-peptide concentration - time curve within 10 to 120 min after
iv glucose challenge
AUCC-PEP (0-120min) Area under the C-peptide concentration - time curve within 0 to 120 min after iv
glucose challenge
AUCGLU(0-120min) Area under the plasma glucose concentration - time curve within 0 to 120 min
after iv glucose challenge
Key secondary endpoints [13C-MMTT (both breakfast and late lunch)-related]
AUCGLU(0-240min) Area under the plasma glucose concentration - time curve within 0 to 240 min
after starting meal ingestion
AUCINS(0-240min) Area under the plasma insulin concentration - time curve within 0 to 240 min
after starting meal ingestion
AUCC-PEP(0-240 min) Area under the plasma C-peptide concentration - time curve within 0 to 240 min
after starting meal ingestion
AUCGCN(0-240min) Area under the plasma glucagon concentration - time curve within 0 to 240 min
after starting meal ingestion
AUCFFA(0-240min) Area under the serum free fatty acid concentration - time curve within 0 to 240
min after starting meal Ingestion
AUCTG(0-240min) Area under the serum triglyceride concentration - time curve within 0 to 240 min
after starting meal ingestion
t1/2, tlag, GEC Mean half emptying time (t1/2 ), lag phase (tlag) and gastric emptying coefficient
(GEC) after meal
Fasting plasma glucose (FPG), SMPG, 7-point SMPG profiles, fasting cholesterol, LDL and HDL, HbA1c,
body weight
Secondary endpoints (safety)
Clinical laboratory, ECG parameters, vital signs, adverse events and serious adverse events (including
in particular symptomatic and severe symptomatic hypoglycemia, local intolerability at injection site,
allergic or allergic-like reactions, suspected pancreatitis and major cardiovascular events).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
We compare the combined treatment (Lantus and Lyxumia) to the single treatments. |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |