A Study That Will Evaluate Ketogenesis and Glucose-Dependent Insulin Secretion Methodologies in Healthy Male Subjects (MK-0000-159)(COMPLETED)

NCT01055340 | Completed Phase 1

• 3 other identifiers: 0000-1591592010_506
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will test the hypotheses that a single dose of oxyntomodulin (OXM) will be neutral or better than placebo in lowering ambient glucose levels during a graded glucose infusion (GGI) and that a single dose of OXM will lead to a statistically significant increase in the sum of the plasma βOHB + AcAc levels compared to placebo.

Conditions

Obesity

Keywords

Ketogenesis; Glucose-Dependent Insulin Secretion; Graded Glucose Infusion; Oxyntomodulin

Outcome Measures

Primary Outcomes (2)

• Ambient plasma glucose concentration during the GGI

  Last 160 minutes of OXM/placebo infusion

• plasma βOHB + AcAc concentrations

  First 300 minutes of OXM/placebo infusion

Study Arms (6)

Treatment sequence 1

EXPERIMENTAL

OXM 3.0 pmol/kg/min - OXM 0.6 pmol/kg/min - Placebo

Drug: Oxyntomodulin (OXM); Drug: Comparator: Oxyntomodulin (OXM); Drug: Comparator: Placebo [ hemaccel-containing saline]

Treatment sequence 2

EXPERIMENTAL

OXM 0.6 pmol/kg/min - Placebo - OXM 3.0 pmol/kg/min

Drug: Oxyntomodulin (OXM); Drug: Comparator: Oxyntomodulin (OXM); Drug: Comparator: Placebo [ hemaccel-containing saline]

Treatment sequence 3

EXPERIMENTAL

Placebo - OXM 3.0 pmol/kg/min - OXM 0.6 pmol/kg/min

Drug: Oxyntomodulin (OXM); Drug: Comparator: Oxyntomodulin (OXM); Drug: Comparator: Placebo [ hemaccel-containing saline]

Treatment sequence 4

EXPERIMENTAL

OXM 3.0 pmol/kg/min - Placebo - OXM 0.6 pmol/kg/min

Drug: Oxyntomodulin (OXM); Drug: Comparator: Oxyntomodulin (OXM); Drug: Comparator: Placebo [ hemaccel-containing saline]

Treatment sequence 5

EXPERIMENTAL

Placebo - OXM 0.6 pmol/kg/min - OXM 3.0 pmol/kg/min

Drug: Oxyntomodulin (OXM); Drug: Comparator: Oxyntomodulin (OXM); Drug: Comparator: Placebo [ hemaccel-containing saline]

Treatment sequence 6

EXPERIMENTAL

OXM 0.6 pmol/kg/min - OXM 3.0 pmol/kg/min - Placebo

Drug: Oxyntomodulin (OXM); Drug: Comparator: Oxyntomodulin (OXM); Drug: Comparator: Placebo [ hemaccel-containing saline]

Interventions

Oxyntomodulin (OXM) DRUG

Single infusion of OXM 3.0 pmol/kg/min by IV

Treatment sequence 1; Treatment sequence 2; Treatment sequence 3; Treatment sequence 4; Treatment sequence 5; Treatment sequence 6

Comparator: Oxyntomodulin (OXM) DRUG

Single infusion of OXM 0.6 pmol/kg/min by IV

Treatment sequence 1; Treatment sequence 2; Treatment sequence 3; Treatment sequence 4; Treatment sequence 5; Treatment sequence 6

Comparator: Placebo [ hemaccel-containing saline] DRUG

Single Placebo infusion of hemaccel-containing saline by IV

Treatment sequence 1; Treatment sequence 2; Treatment sequence 3; Treatment sequence 4; Treatment sequence 5; Treatment sequence 6

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is judged to be in good health based on medical history, physical examination, and laboratory safety tests
• Subject has a Body Mass Index of ≥27 kg/m\^2 and ≤35 kg/m\^2 and weighs ≥70 kg at the prestudy (screening) visit
• Subject has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months
• Subject is willing to avoid strenuous physical activity (weight lifting, running, bicycling, etc.) for the duration of the study

You may not qualify if:

• Subject is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit
• Subject has a history of stroke, chronic seizures, or major neurological disorder
• Subject has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
• Subject has irritable bowel disease, or recurrent occurrences of nausea, vomiting, diarrhea, or abdominal pain
• Subject has a history of hypertension requiring treatment
• Subject has a history of cancer
• Subject has history of diabetes, or family history of diabetes mellitus
• Subject has a history of hypersensitivity to OXM or hemaccel

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• 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.

  PMID: 29545266 DERIVED

• 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.

  PMID: 27072496 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Oxyntomodulin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2010
• First Posted: January 25, 2010
• Study Start: April 1, 2010
• Primary Completion: May 1, 2010
• Study Completion: June 1, 2010
• Last Updated: May 29, 2015

Record last verified: 2015-05