Clinical trial NCT01373450: 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)
Official title: Evaluation of the Glucoregulatory Effects of GLP-1 Receptor Activation in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-06-15
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Change From Baseline in Time-weighted Average of Glucose Measured by Area Under the Curve (AUC) After a Single Dose of Oxyntomodulin (OXM)
timeFrame: Baseline and during GGI at time points 0, 20, 40, 60, 80, 100, 120, 140, 160 and 165 minutes
measure: Change From Baseline in Maximum Ambient Glucose Concentration (Gmax) After a Single Dose of OXM
timeFrame: Baseline and up to 160 minutes after start of GGI
measure: Change From Baseline in Beta Cell Sensitivity to Glucose (Φ) After a Single Dose of OXM
timeFrame: Baseline and up to160 minutes after start of GGI
Secondary outcomes:
measure: Change From Baseline in Insulinotrophic Effect (ISR/G) at the Highest Glucose Infusion Rate After Two Periods of Placebo Treatment
timeFrame: Baseline and 160 minutes after start of GGI at each placebo treatment period
measure: Change From Baseline in Gmax After Single Doses of 0.6 mg Lg, or 1.2 mg Lg, Compared With Single Doses of Placebo or OXM
timeFrame: Baseline and up to 160 minutes after start of GGI
measure: Change From Baseline in Insulinotrophic Effect (ISR/G) After Single Doses of 0.6 mg Lg, or 1.2 mg Lg, Compared With Single Doses of Placebo or OXM
timeFrame: Baseline and up to 160 minutes after start of GGI
Other outcomes:
Locations:
Study officials:
References:
citation: 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.
citation: 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.