Type 2 diabetes mellitus MedDRA version: 14.0 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Hustenstiller-ratiopharm Dextromethorphan
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: DEXTROMETHORPHAN HYDROBROMIDE
CAS Number: 125-69-9
Concentration unit: mg milligram(s)
Con
Sponsors
Profil Institut für Stoffwechselforschung GmbH
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Male with T2DM on a stable regimen of metformin monotherapy, between 45 and 70 years of age, with a BMI between 25 and 35 kg/m2, HbA1c between 6.5 and 8% (extremes included). Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4 ;Inclusion criteria: Male with T2DM on a stable regimen of metformin monotherapy, between 45 and 70 years of age, with a BMI between 25 and 35 kg/m2, HbA1c between 6.5 and 8% (extremes included). Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: - Subjects with type 1 diabetes, maturity onset diabetes of the young (MODY) or secondary forms of diabetes such as due to pancreatitis - Current or previous treatment with insulin therapy - Treatment with any hypoglycaemic medication other than metformin within the three months prior to screening - Any severe medical or surgical history of conditions likely to confound study assessments or study endpoints - Serious respiratory, serious and/or unstable coronary heart disease, congestive heart failure of New York Heart Association Class II or worse, second/third degree heart block, superior vena cava syndrome, uncontrolled hypertension, history of stroke (within the preceding 6 months) or serious peripheral vascular disease - History of arrhythmia that is symptomatic or requires treatment - Marked diabetic complications - Any respiratory disease leading to respiratory insufficiency and/or depression - Clinically significant vital signs or 12-lead ECG findings - Clinical or laboratory evidence of hepatic dysfunction or disease - Moderate or severe renal dysfunction defined as a calculated GFR <70 ml/min - Uncontrolled high blood pressure - History of relevant drug and/or food allergies or a history of severe anaphylactic reaction - Use of concomitant medication which would confound study conduct ;Exclusion criteria: - Subjects with type 1 diabetes, maturity onset diabetes of the young (MODY) or secondary forms of diabetes such as due to pancreatitis - Current or previous treatment with insulin therapy - Treatment with any hypoglycaemic medication other than metformin within the three months prior to screening - Any severe medical or surgical history of conditions likely to confound study assessments or study endpoints - Serious respiratory, serious and/or unstable coronary heart disease, congestive heart failure of New York Heart Association Class II or worse, second/third degree heart block, superior vena cava syndrome, uncontrolled hypertension, history of stroke (within the preceding 6 months) or serious peripheral vascular disease - History of arrhythmia that is symptomatic or requires treatment - Marked diabetic complications - Any respiratory disease leading to respiratory insufficiency and/or depression - Clinically significant vital signs or 12-lead ECG findings - Clinical or laboratory evidence of hepatic dysfunction or disease - Moderate or severe renal dysfunction defined as a calculated GFR <70 ml/min - Uncontrolled high blood pressure - History of relevant drug and/or food allergies or a history of severe anaphylactic reaction - Use of concomitant medication which would confound study conduct
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of this trial is to demonstrate that dextromethorphan (DXM) and amantadine compared to placebo exert blood glucose (BG) lowering effects following an oral glucose tolerance test (OGTT) in male subjects with T2DM;Secondary Objective: - To compare other pharmacodynamic (PD) properties (based on glucose, insulin, C-peptide and catecholamine measurements) of oral DXM and amantadine (termed: Investigational Medicinal Product – IMP) before and during an OGTT - For dextromethorphan: to assess whether a dose-dependency of PD exists -To compare the pharmacokinetic (PK) exposure to DXM and metabolites following an oral DXM dose for 5h post-dosing -To assess the PK/PD relationship (based on AUCDXM and AUCglucose) - To assess the safety after single oral dosing ;Primary end point(s): The primary (PD) endpoint of the study is the area under the blood glucose (BG) concentration-time profile.;Timepoint(s) of evaluation of this end point: From 1-3 hours post-dose (i.e. from 0-2 hours after an OGTT);Main Objective: The purpose of this trial is to demonstrate that dextromethorphan (DXM) and amantadine compared to placebo exert blood glucose (BG) lowering effects following an oral glucose tolerance test (OGTT) in male subjects with T2DM;Secondary Objective: - To compare other pharmacodynamic (PD) properties (based on glucose, insulin, C-peptide and catecholamine measurements) of oral DXM and amantadine (termed: Investigational Medicinal Product – IMP) before and during an OGTT - For dextromethorphan: to assess whether a dose-dependency of PD exists -To compare the pharmacokinetic (PK) exposure to DXM and metabolites following an oral DXM dose for 5h post-dosing -To assess the PK/PD relationship (based on AUCDXM and AUCglucose) - To assess the safety after single oral dosing ;Primary end point(s): The primary (PD) endpoint of the study is the area under the blood glucose (BG) concentration-time profile.;Timepoint(s) of evaluation of this end point: From 1-3 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Secondary PD endpoints: 1. from 0-1 hour post-dose 2. from 1-5 hours post-dose 3. from 1-1.5 hours post-dose 4. after starting the OGTT 5. after an OGTT 6. after an OGTT 7. from 0-1 hour post-dose 8. from 1-1.5 hours post-dose 9. from 1-5 hours post-dose 10. from 1-3 hours post-dose 11. after an OGTT 12. after an OGTT 13. from 1-5 hours post-dose 14. from 0-1 hour post-dose Secondary PK endpoints: 1. from 0-1 hour post-dose 2. from 1-5 hours post-dose 3. from 0-1 hour post-dose 4. from 1-5 hours post-dose 5. from 0-1 hour post-dose 6. from 1-5 hours post-dose 7. from 0-1 hour post-dose 8. from 1-5 hours post-dose ;Secondary end point(s): Secondary PD endpoints: 1. Area under the blood glucose concentration-time profile 2. Area under the blood glucose concentration-time profile 3. Area under the blood glucose concentration-time profile 4. maximum blood glucose excursion 5. maximum blood glucose concentration 6. time to maximum blood glucose concentration 7. Area under the plasma insulin concentration-time profile 8. Area under the plasma insulin concentration-time profile 9. Area under the plasma insulin concentration-time profile 10. Area under the plasma insulin concentration-time profile 11. Maximum plasma insulin concentration 12. Time to maximum plasma insulin concentration 13. area under the catecholamine (adrenaline, noradrenaline) concentration-time profile 14. catecholamine excursions Secondary PK endpoints: 1. Area under the plasma DXM concentration-time profile 2. Area under the plasma DXM concentration-time profile 3. Area under the plasma HM concentration-time profile 4. Area under the plasma HM concentration-time profile 5. Area under the plasma DX concentration-time profile 6. Area under the plasma DX concentration-time profile 7. Area under the plasma MM concentration-time profile 8. Area under the plasma MM concentration-ti | — |
Countries
Germany
Contacts
Public ContactRegulatory Affairs;Regulatory Affairs ;
Profil Institut für Stoffwechselforschung GmbH;Profil Institut für Stoffwechselforschung GmbH
Outcome results
None listed