A Study to Investigate the Glucose Lowering Effects of Dextromethorphan Alone or in Combination With Sitagliptin in Subjects With Type 2 Diabetes Mellitus (T2DM) After an Oral Glucose Tolerance Test

Phase 2

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Dextromethorphan; Drug: Placebo; Drug: Sitagliptin

• Registration Number: NCT01936025
• Lead Sponsor: Profil Institut für Stoffwechselforschung GmbH

Brief Summary

The study has a randomized, double-blind, placebo-controlled, double dummy and eight-way cross-over design. Males with T2DM on a stable metformin monotherapy will be screened for participation in the study. Eligible subjects will be randomized to receive DXM 30 mg, DXM 60 mg, DXM 90 mg alone or in combination with sitagliptin 100 mg, sitagliptin 100 mg alone, or placebo (for DXM and sitagliptin) on in total eight treatment days. An OGTT will be started 1 hour after study drug administration and blood glucose will be measured over the next 4 hours. There will be a 3 to 14-day washout period between doses.

Detailed Description

This study is performed to determine the optimal dose of DXM that, compared to placebo, decreases glucose excursions following an OGTT. Doses of 30 mg, 60 mg and 90 mg DXM were chosen. Since DXM 60 mg was effective in the previous study in increasing insulin secretion, this dose will be kept. A lower dose (30 mg) will be given to see whether effects on insulin secretion are present also at lower doses and then translate into a BG lowering action. A higher dose (90 mg) will be added to see whether this way an effect on glucose excursion reduction occurs following an OGTT, (like previously demonstrated with 270 mg DXM) that can be related to an increase of insulin secretion.

Study Timeline

• Study First Submitted: 2013-08-28
• Study First Submitted QC: 2013-09-02
• Study First Posted: 2013-09-05
• Study Start: 2013-10
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-06
• Last Update Posted: 2017-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 34

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

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
4. Treatment with any hypoglycemic medication other than metformin within the three months prior to screening
5. Mean QTc> 450 msec

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Dextromethorphan 60 mg + sitagliptin	Dextromethorphan	Dextromethorphan 60 mg + sitagliptin 100 mg
Placebo	Placebo	Placebo (dextromethorphan)+ placebo (sitagliptin)
Sitagliptin	Sitagliptin	Placebo dextromethorphan + sitagliptin 100 mg
Dextromethorphan 30 mg + placebo	Dextromethorphan	Dextromethorphan 30 mg + placebo (sitagliptin)
Dextromethorphan 90 mg + sitagliptin	Sitagliptin	Dextromethorphan 90 mg + sitagliptin 100 mg
Dextromethorphan 30 mg + sitagliptin	Dextromethorphan	Dextromethorphan 30 mg + sitagliptin 100 mg
Dextromethorphan 30 mg + sitagliptin	Sitagliptin	Dextromethorphan 30 mg + sitagliptin 100 mg
Dextromethorphan 60 mg + sitagliptin	Sitagliptin	Dextromethorphan 60 mg + sitagliptin 100 mg
Dextromethorphan 90 mg + sitagliptin	Dextromethorphan	Dextromethorphan 90 mg + sitagliptin 100 mg
Dextromethorphan 60 mg + placebo	Dextromethorphan	Dextromethorphan 60 mg + placebo (sitagliptin)
Dextromethorphan 90 mg + placebo	Dextromethorphan	Dextromethorphan 90 mg + placebo (sitagliptin)

Primary Outcome Measures

Name	Time	Method
lowest dose of DXM	up to 4 hours after study drug administration	To find the lowest dose of DXM that, compared to placebo, exerts BG lowering effects related to an OGTT

Secondary Outcome Measures

Name	Time	Method
additive BG lowering effects	up to 4 hours after study drug administration	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

Trial Locations

Locations (1)

Profil Institut für Stoffwechselforschung GmbH; 🇩🇪 Neuss, Germany