Dextromethorphan, Amantadine and Glucose Homeostasis in Diabetes Subjects

NCT01441986 | Completed Phase 2 DMC

• 1 other identifier: 0533-DXM
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

dextromethorphan; amantadine; blood glucose lowering effect; oral glucose tolerance test

Outcome Measures

Primary Outcomes (1)

• Area under the blood glucose (BG) concentration-time profile

  from 1-3 hours post-dose (i.e. from 0-2 hours after an OGTT)

Secondary Outcomes (2)

• Area under the blood glucose concentration-time profile

  0-1 hour post-dose (i.e. before starting the OGTT)

• Adverse events

  5 hours post-dose

Interventions

Dextromethorphan hydrobromide DRUG

Dextromethorphan hydrobromide•1 H2O; 30 mg; hard capsules; single, oral dose.

Also known as: Dextromethorphan, Ratiopharm GmbH

Amantadine DRUG

Amantadine hydrochloride 100 mg; tablets; single, oral dose.

Also known as: Amantadine, STADA Arzneimittel AG.

Pacebo 1 (placebo for Amantadine) DRUG

Talets for oral use; single dose.

Also known as: P-Tabletten weiß 10 mm Lichtenstein, Winthrop Arzneimittel.

Placebo 2 (fo Dextromethorphan) DRUG

Capsles for oral administration; single dose.

Also known as: Empty capsules, Capsugel Bornem Belgium.

Eligibility Criteria

• Age: 45 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male subjects with a diagnosis of type 2 diabetes mellitus according to ADA criteria at least 4 months prior to screening
• Medical history without major pathology (with the exception of type 2 diabetes)
• On a stable regimen of metformin monotherapy for at least 3 months
• Body mass index (BMI) between 25 and 35kg/m2, both inclusive
• HbA1c ≥ 6.5 and \<7.5%
• A male subject who is sexually active and not surgically sterilised, must agree to use adequate contraceptive methods from the time of first study drug administration until 90 days after last dosing.
• 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.

You may not qualify if:

• 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 (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)
• Treatment with any hypoglycaemic medication other than metformin within the three months prior to screening
• 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
• 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
• History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (grade 3), left bundle branch block, or asymptomatic sustained ventricular tachycardia are not allowed
• Marked diabetic complications: severe autonomic or sensory neuropathy including gastroparesis; proliferative retinopathy
• Any respiratory disease leading to respiratory insufficiency and/or depression including but not limited to: asthma bronchiale, chronic obstructive pulmonary disease.
• Clinically significant vital signs including known bradycardia with pulse rate \< 55/min or 12-lead ECG findings including pre-treatment QTc \> 420 msec (if the ECG shows a QTc value of \> 420 ms, two further ECGs will be repeated within the next 30 minutes, at least 2 minutes apart, with the mean value of these 3 consecutive ECGs being conclusive).
• History of or current prostata hyperplasia
• History of or current narrow angle glaucoma
• Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis or coagulation screening tests, as judged by the Investigator
• Moderate or severe renal dysfunction defined as a calculated GFR \< 70 ml/min using the Cockcroft-Gault calculation
• Clinical or laboratory evidence of hepatic dysfunction or disease; laboratory evidence defined as any of the following parameters: alkaline phosphatase \> 2x upper limit of normal (ULN), ALT \> 2x ULN, AST \> 2x ULN or bilirubin \> 3x ULN. Isolated mild rise in bilirubin considered to be due to Gilbert's condition is allowed
• Uncontrolled high blood pressure (DBP \> 95 mmHg and/or SBP \> 160 mmHg), unless clearly documented to be white-coat hypertension

Sponsors & Collaborators

• Profil Institut für Stoffwechselforschung GmbH: lead
• Heinrich-Heine University, Duesseldorf: collaborator

Study Sites (1)

Profil Institute for Metabolic Research

Neuss, North Rhine-Westphalia, 41460, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Dextromethorphan; Amantadine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Alin O Stirban, MD

  Profil Institute for Metabolic Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2011
• First Posted: September 28, 2011
• Study Start: September 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: July 12, 2012

Record last verified: 2012-07

Locations

DE (1)