Evaluation of the Glucoregulatory Effects of Glucagon-like Peptide-1 Receptor (GLP-1 Receptor) Activation in Participants With Type 2 Diabetes Mellitus (MK-0000-222)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Oxyntomodulin; Drug: Liraglutide 0.6 mg; Drug: Placebo for Oxyntomodulin; Drug: Placebo for Liraglutide; Drug: Liraglutide 1.2 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01373450

0000-222

Details and patient eligibility

About

This was a four-period crossover study to assess the glycemic effects of a single dose of oxyntomodulin (OXM) on the glucose levels in participants with Type 2 diabetes mellitus (T2DM). Participants were randomly assigned to 1 of 6 treatment sequences consisting of 4 treatment periods, with a 7-day wash-out between each treatment period. The primary hypothesis was that during graded glucose infusion (GGI) oxyntomodulin (OXM) is neutral or better than placebo (Pbo) at lowering ambient plasma glucose levels, and at significantly enhancing insulin secretion.

Enrollment: 12 patients

Sex: Male

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have a body mass index (BMI) of ≤38.0 kg/m^2
• Have a clinical diagnosis of Type 2 diabetes mellitus
• Have a glycated hemoglobin (HbA1C) at screening ≤9.0%; fasting plasma glucose should not exceed 300 mg/dL (16.8 mmol/L)
• Judged to be in good health

Exclusion criteria

• Have a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the subject by their participation in the study
• Have a history of stroke, chronic seizures, major neurological disorder, clinically significant endocrine, cardiovascular, hematological, hepatic, renal, respiratory, or genitourinary abnormalities or diseases
• Have untreated hypertension with blood pressure of >160/95 mmHg
• Have a history of neoplastic disease within the past 5 years
• Have a history of hypersensitivity to OXM, liraglutide, insulin or Haemaccel®
• Unable or unwilling to comply with restrictions around concomitant medications
• Consume excessive amounts of alcohol, coffee, tea, cola, or other caffeinated beverages daily
• Have had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks
• Have a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Currently a regular user (including use of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 3 months
• Are unwilling or unable to consume the standardized meals during the study and/or is on a carbohydrate restricted diet (i.e., a diet <100 grams per day of carbohydrate)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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12 participants in 6 patient groups

OXM → Lg-0.6 → Pbo → Lg-1.2

Experimental group

Description:

Participants received Oxyntomodulin 3.0 pmol/kg/min in the first, Liraglutide 0.6 mg in the second, Placebo in the third, and Liraglutide 1.2 mg in the fourth period

Treatment:

Drug: Placebo for Liraglutide

Drug: Placebo for Oxyntomodulin

Drug: Liraglutide 0.6 mg

Drug: Oxyntomodulin

Lg-0.6 → Pbo → OXM → Pbo

Experimental group

Description:

Participants received Liraglutide 0.6 mg in the first, Placebo in the second, Oxyntomodulin 3.0 pmol/kg/min in the third, and Placebo in the fourth period

Treatment:

Drug: Placebo for Liraglutide

Drug: Placebo for Oxyntomodulin

Drug: Liraglutide 0.6 mg

Drug: Oxyntomodulin

Pbo → OXM → Lg-0.6 → Pbo

Experimental group

Description:

Participants received Placebo in the first, Oxyntomodulin 3.0 pmol/kg/min in the second, Liraglutide 0.6 mg in the third, and Placebo in the fourth period

Treatment:

Drug: Placebo for Liraglutide

Drug: Placebo for Oxyntomodulin

Drug: Liraglutide 0.6 mg

Drug: Oxyntomodulin

Lg-0.6 → OXM → Pbo → Lg-1.2

Experimental group

Description:

Participants received Liraglutide 0.6 mg in the first, Oxyntomodulin 3.0 pmol/kg/min in the second, Placebo in the third and Liraglutide 1.2 mg in the fourth period

Treatment:

Drug: Liraglutide 1.2 mg

Drug: Placebo for Liraglutide

Drug: Placebo for Oxyntomodulin

Drug: Liraglutide 0.6 mg

Drug: Oxyntomodulin

OXM → Pbo → Lg-0.6 → Pbo

Experimental group

Description:

Participants received Oxyntomodulin 3.0 pmol/kg/min in the first; Placebo in the second, Liraglutide 0.6 mg in the third, and Placebo in the fourth period

Treatment:

Drug: Placebo for Liraglutide

Drug: Placebo for Oxyntomodulin

Drug: Liraglutide 0.6 mg

Drug: Oxyntomodulin

Pbo → Lg-0.6 → OXM → Lg-1.2

Experimental group

Description:

Participants received Placebo in the first, Liraglutide 0.6 mg in the second, Oxyntomodulin 3.0 pmol/kg/min in the third, and Liraglutide 1.2 mg in the fourth period

Treatment:

Drug: Liraglutide 1.2 mg

Drug: Placebo for Liraglutide

Drug: Placebo for Oxyntomodulin

Drug: Liraglutide 0.6 mg

Drug: Oxyntomodulin