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)

NCT ID: NCT01373450

Last Updated: 2015-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2011-07-31

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

OXM → Lg-0.6 → Pbo → Lg-1.2

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

Group Type: EXPERIMENTAL

Oxyntomodulin

Intervention Type: DRUG

3.0 pmol/kg/min as an intravenous (IV) infusion in the morning of the day of graded glucose infusion (GGI) (Day 1)

Liraglutide 0.6 mg

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Placebo for Oxyntomodulin

Intervention Type: DRUG

IV infusion in the morning of the day of GGI (Day 1)

Placebo for Liraglutide

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Lg-0.6 → Pbo → OXM → Pbo

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

Group Type: EXPERIMENTAL

Oxyntomodulin

Intervention Type: DRUG

3.0 pmol/kg/min as an intravenous (IV) infusion in the morning of the day of graded glucose infusion (GGI) (Day 1)

Liraglutide 0.6 mg

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Placebo for Oxyntomodulin

Intervention Type: DRUG

IV infusion in the morning of the day of GGI (Day 1)

Placebo for Liraglutide

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Pbo → OXM → Lg-0.6 → Pbo

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

Group Type: EXPERIMENTAL

Oxyntomodulin

Intervention Type: DRUG

3.0 pmol/kg/min as an intravenous (IV) infusion in the morning of the day of graded glucose infusion (GGI) (Day 1)

Liraglutide 0.6 mg

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Placebo for Oxyntomodulin

Intervention Type: DRUG

IV infusion in the morning of the day of GGI (Day 1)

Placebo for Liraglutide

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Lg-0.6 → OXM → Pbo → Lg-1.2

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

Group Type: EXPERIMENTAL

Oxyntomodulin

Intervention Type: DRUG

3.0 pmol/kg/min as an intravenous (IV) infusion in the morning of the day of graded glucose infusion (GGI) (Day 1)

Liraglutide 0.6 mg

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Liraglutide 1.2 mg

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Placebo for Oxyntomodulin

Intervention Type: DRUG

IV infusion in the morning of the day of GGI (Day 1)

Placebo for Liraglutide

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

OXM → Pbo → Lg-0.6 → Pbo

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

Group Type: EXPERIMENTAL

Oxyntomodulin

Intervention Type: DRUG

3.0 pmol/kg/min as an intravenous (IV) infusion in the morning of the day of graded glucose infusion (GGI) (Day 1)

Liraglutide 0.6 mg

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Placebo for Oxyntomodulin

Intervention Type: DRUG

IV infusion in the morning of the day of GGI (Day 1)

Placebo for Liraglutide

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Pbo → Lg-0.6 → OXM → Lg-1.2

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

Group Type: EXPERIMENTAL

Oxyntomodulin

Intervention Type: DRUG

3.0 pmol/kg/min as an intravenous (IV) infusion in the morning of the day of graded glucose infusion (GGI) (Day 1)

Liraglutide 0.6 mg

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Liraglutide 1.2 mg

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Placebo for Oxyntomodulin

Intervention Type: DRUG

IV infusion in the morning of the day of GGI (Day 1)

Placebo for Liraglutide

Intervention Type: DRUG

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Interventions

Oxyntomodulin

3.0 pmol/kg/min as an intravenous (IV) infusion in the morning of the day of graded glucose infusion (GGI) (Day 1)

Intervention Type: DRUG

Liraglutide 0.6 mg

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Intervention Type: DRUG

Liraglutide 1.2 mg

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Intervention Type: DRUG

Placebo for Oxyntomodulin

IV infusion in the morning of the day of GGI (Day 1)

Intervention Type: DRUG

Placebo for Liraglutide

Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Intervention Type: DRUG

Other Intervention Names

Victoza®; Victoza®

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Shankar SS, Shankar RR, Mixson LA, Miller DL, Pramanik B, O'Dowd AK, Williams DM, Frederick CB, Beals CR, Stoch SA, Steinberg HO, Kelley DE. Native Oxyntomodulin Has Significant Glucoregulatory Effects Independent of Weight Loss in Obese Humans With and Without Type 2 Diabetes. Diabetes. 2018 Jun;67(6):1105-1112. doi: 10.2337/db17-1331. Epub 2018 Mar 15.

Reference Type: DERIVED

PMID: 29545266 (View on PubMed)

Shankar SS, Shankar RR, Mixson LA, Miller DL, Chung C, Cilissen C, Beals CR, Stoch SA, Steinberg HO, Kelley DE. Linearity of beta-cell response across the metabolic spectrum and to pharmacology: insights from a graded glucose infusion-based investigation series. Am J Physiol Endocrinol Metab. 2016 Jun 1;310(11):E865-73. doi: 10.1152/ajpendo.00527.2015. Epub 2016 Apr 12.

Reference Type: DERIVED

PMID: 27072496 (View on PubMed)

Other Identifiers

0000-222

Identifier Type: -

Identifier Source: org_study_id