Diabetes mellitus MedDRA version: 16.0 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Hustenstiller-ratiopharm® Dextromethorphan
Product Name: Hustenstiller-ratiopharm® Dextromethorphan
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Dextromethorphanhydrobromid
CAS
Sponsors
Profil Institut für Stoffwechselforschung GmbH
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Signed and dated written informed consent obtained before any study-related activities 2. Male subjects with a diagnosis of type 2 diabetes mellitus according to ADA criteria at least 4 months prior to screening 3. Medical history without major pathology (with the exception of type 2 diabetes) 4. On a stable regimen of metformin monotherapy for at least 3 months 5. Aged between 45 and 70 years of age, both inclusive 6. Body mass index (BMI) between 25 and 35kg/m2, both inclusive 7. HbA1c 6.5 and 8.0% 8. A male subject who is sexually active and not surgically sterilized, must agree to use adequate contraceptive methods as described in Section 3.3.2.1 from the time of first study drug administration until the end of the study. 9. Ability and willingness to abstain from grapefruit juice (and all grapefruit containing products) throughout the study starting 24 hours prior to first study drug administration and from alcohol, methylxanthine-containing beverages or food (coffee, tea, Coke, chocolate, “power drinks”), tobacco products and from engaging in strenuous physical activity from 24 hours prior to each admission until discharge from the unit. 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Subjects with type 1 diabetes, MODY or secondary forms of diabetes such as due to pancreatitis 2. History of pancreatitis 3. Current or previous treatment with insulin therapy (except for treatment within a clinical trial, for surgical procedures or during an acute illness for 1 month and more than 3 months before the first administration of study drug) 4. Treatment with any hypoglycemic medication other than metformin within the three months prior to screening 5. Mean QTc> 450 msec for male (Bazett formula, mean value of 3 consecutive ECGs) 6. Subjects with any severe medical or surgical history of conditions likely to confound study assessments or study endpoints, for example but not limited to haemoglobinopathies, inflammatory bowel disease, cystic fibrosis, bariatric surgery and/or any surgery shortening the intestine, history of galactose intolerance, lactose- or glucose-galactose-malabsorption 7. Serious respiratory, serious and/or unstable coronary heart disease (unstable angina, myocardial infarction within the preceding 6 months), congestive heart failure of New York Heart Association Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnoea), second/third degree heart block, superior vena cava syndrome, uncontrolled hypertension, history of congenital QT-syndrome within family, history of stroke (within the preceding 6 months) or serious peripheral vascular disease as judged by the investigator 8. Marked diabetic complications: severe autonomic or sensory neuropathy including gastroparesis; proliferative retinopathy as judged by the investigator 9. Any respiratory disease leading to respiratory insufficiency and/or depression including but not limited to: asthma bronchiale, chronic obstructive pulmonary disease, as judged by the investigator 10. Clinically significant vital signs including bradycardia with pulse rate < 50/min 11. Subjects with a history, a suspicion, or a family history of medullary thyroid cancer or a multiple endocrine neoplasia 12. Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis or coagulation screening tests, as judged by the Investigator 13. Moderate or severe renal dysfunction defined as a calculated GFR <60ml/min using the MDRD calculation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: First primary objective: to find the lowest dose of DXM that, compared to placebo, exerts BG lowering effects related to an OGTT Second primary objective: to demonstrate whether the administration of DXM on top of sitagliptin exerts additive BG lowering effects related to an OGTT as compared to sitagliptin alone and DXM alone.;Secondary Objective: - To compare other pharmacodynamic (PD) properties (based on glucose, insulin and possibly C-peptide and glucagon measurements) of oral DXM alone or on top of sitagliptin (termed: Investigational Medicinal Product – IMP) before and after starting an OGTT. Comparisons will be made as follows: - DXM different doses compared with placebo for DXM - DXM different doses + sitagliptin 100 mg compared with DXM alone corresponding doses - DXM different doses + sitagliptin 100 mg compared with sitagliptin alone - effective DXM doses (at least 10% higher effect than placebo) compared to sitagliptin 100 mg - To compare the pharmacokinetic (PK) exposure to DXM and dextrorphan (DX) following an oral DXM dose for 5h post-dosing - To assess the safety and tolerability after single oral dosing for DXM alone or in combination with sitagliptin;Primary end point(s): AUCBG(1-3h): area under the blood glucose (BG) concentration-time profile from 1-3 hours post-dose (i.e. from 0-2 hours after starting the OGTT);Timepoint(s) of evaluation of this end point: With occasion of each of the 8 investigations | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): AUCBG(0-1h) area under the blood glucose concentration-time profile from 0-1 hour post-dose (i.e. before starting the OGTT) AUCBG(1-5h) area under the blood glucose concentration-time profile from 1-5 hours post-dose (i.e. 0-4h after starting the OGTT) AUCBG(1-1.5h) area under the blood glucose concentration-time profile from 1-1.5 hours post-dose (i.e. from 0-30 min after starting the OGTT) Pameters after starting the OGTT: ?BGmax BGmax tBGmax AUCINS(0-1h) AUCINS(1-1.5h) AUCINS(1-3-5h) AUCINS(1-5h) INSmax INSmean tINSmax AUCGGN(1-5h) area under the glucagon concentration-time profile from 1-5 hours post-dose (i.e. from 0-4 hours after starting the OGTT) ?GGN(0-1h) glucagon excursions from 0-1 hour post-dose (i.e. before OGTT) AUCBG(1-1.5h)xAUCINS(1-1.5h) hepatic insulin resistance index ?Glucose120-300min/?t x INSmean muscle insulin sensitivity index;Timepoint(s) of evaluation of this end point: With occasion of each of the 8 investigations | — |
Countries
Germany
Contacts
Public ContactRegulatory Affairs
Profil Institut für Stoffwechselforschung GmbH
Outcome results
None listed