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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase IIa, Dose-finding, Double-blind, Placebo-controlled, Double-dummy, Randomized, Eightfold Cross-over 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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dextromethorphan
* Drug: Sitagliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated written informed consent obtained before any study-related activities 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 Aged between 45 and 70 years of age, both inclusive Body mass index (BMI) between 25 and 35kg/m2, both inclusive Exclusion Criteria: Subjects with type 1 diabetes, MODY or secondary forms of diabetes such as due to pancreatitis History of pancreatitis Current or previous treatment with insulin therapy Treatment with any hypoglycemic medication other than metformin within the three months prior to screening Mean QTc> 450 msec

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sitagliptin<br>Placebo dextromethorphan + sitagliptin 100 mg | Drug: Sitagliptin<br> <br> |
| Experimental: Dextromethorphan 30 mg + sitagliptin<br>Dextromethorphan 30 mg + sitagliptin 100 mg | Drug: Dextromethorphan<br> <br> Drug: Sitagliptin<br> <br> |
| Experimental: Dextromethorphan 60 mg + sitagliptin<br>Dextromethorphan 60 mg + sitagliptin 100 mg | Drug: Dextromethorphan<br> <br> Drug: Sitagliptin<br> <br> |
| Experimental: Dextromethorphan 90 mg + sitagliptin<br>Dextromethorphan 90 mg + sitagliptin 100 mg | Drug: Dextromethorphan<br> <br> Drug: Sitagliptin<br> <br> |
| Experimental: Dextromethorphan 30 mg + placebo<br>Dextromethorphan 30 mg + placebo (sitagliptin) | Drug: Dextromethorphan<br> <br> |
| Experimental: Dextromethorphan 60 mg + placebo<br>Dextromethorphan 60 mg + placebo (sitagliptin) | Drug: Dextromethorphan<br> <br> |
| Experimental: Dextromethorphan 90 mg + placebo<br>Dextromethorphan 90 mg + placebo (sitagliptin) | Drug: Dextromethorphan<br> <br> |
| Placebo Comparator: Placebo<br>Placebo (dextromethorphan)+ placebo (sitagliptin) | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lowest dose of DXM | To find the lowest dose of DXM that, compared to placebo, exerts BG lowering effects related to an OGTT | up to 4 hours after study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| additive BG lowering effects | 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 | up to 4 hours after study drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes mellitus