Type 2 Diabetes MellitusPhase 1NCT01373450

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)

A Phase 1 study testing Oxyntomodulin, Liraglutide 0.6 mg and Liraglutide 1.2 mg in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 64 years, men only
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: Oxyntomodulin, Liraglutide 0.6 mg and Liraglutide 1.2 mg
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 12 participants
Where: No sites listed yet
Study dates: Jun 2011to Jul 2011
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 64 years
Men only
No healthy volunteers
Adult

Who may be able to join

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

Who cannot join

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

Show all 11Show fewer

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)

About this study

Official title: Evaluation of the Glucoregulatory Effects of GLP-1 Receptor Activation in Patients With Type 2 Diabetes Mellitus

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
Being tested: Oxyntomodulin, Liraglutide 0.6 mg, Liraglutide 1.2 mg, Placebo for Oxyntomodulin, Placebo for Liraglutide
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OxyntomodulinDrug
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 mgDrug
Also called Victoza®
Single subcutaneous dose in the evening of the day before the GGI (Day-1)
Liraglutide 1.2 mgDrug
Also called Victoza®
Single subcutaneous dose in the evening of the day before the GGI (Day-1)
Placebo for OxyntomodulinDrug
IV infusion in the morning of the day of GGI (Day 1)
Placebo for LiraglutideDrug
Single subcutaneous dose in the evening of the day before the GGI (Day-1)

Study groups in NCT01373450
Study group	Role	What they receive
OXM → Lg-0.6 → Pbo → Lg-1.2	Experimental	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 Receives: Drug: Oxyntomodulin; Drug: Liraglutide 0.6 mg; Drug: Placebo for Oxyntomodulin; Drug: Placebo for Liraglutide
Lg-0.6 → Pbo → OXM → Pbo	Experimental	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 Receives: Drug: Oxyntomodulin; Drug: Liraglutide 0.6 mg; Drug: Placebo for Oxyntomodulin; Drug: Placebo for Liraglutide
Pbo → OXM → Lg-0.6 → Pbo	Experimental	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 Receives: Drug: Oxyntomodulin; Drug: Liraglutide 0.6 mg; Drug: Placebo for Oxyntomodulin; Drug: Placebo for Liraglutide
Lg-0.6 → OXM → Pbo → Lg-1.2	Experimental	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 Receives: Drug: Oxyntomodulin; Drug: Liraglutide 0.6 mg; Drug: Liraglutide 1.2 mg; Drug: Placebo for Oxyntomodulin; Drug: Placebo for Liraglutide
OXM → Pbo → Lg-0.6 → Pbo	Experimental	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 Receives: Drug: Oxyntomodulin; Drug: Liraglutide 0.6 mg; Drug: Placebo for Oxyntomodulin; Drug: Placebo for Liraglutide
Pbo → Lg-0.6 → OXM → Lg-1.2	Experimental	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 Receives: Drug: Oxyntomodulin; Drug: Liraglutide 0.6 mg; Drug: Liraglutide 1.2 mg; Drug: Placebo for Oxyntomodulin; Drug: Placebo for Liraglutide

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Time-weighted Average of Glucose Measured by Area Under the Curve (AUC) After a Single Dose of Oxyntomodulin (OXM)
Participants received on Day (-1) an overnight intravenous (IV) infusion of insulin titrated to achieve baseline fasting plasma glucose on Day 1 of between 90 and 130 mg/dL. Participants also received on Day (-1) a single dose of liraglutide (Lg) or placebo for Lg, after which insulin infusion was discontinued. Following overnight fast, participants received on Day 1 OXM or placebo for OXM, accompanied by up to 160 minutes of graded glucose infusion (GGI). During GGI glucose (20% D/W) was gradually infused at rates of 2,4,6 and 10 mg/kg/min, with each rate lasting approximately 40 minutes. Glucose levels were measured from blood collected at baseline and during GGI at the following minutes: 0, 20, 40, 60, 80, 100, 120, 140, 160 and 165 in order to calculate the time-weighted average change from baseline in glucose AUC from 0-160 minutes.
Measured: Baseline and during GGI at time points 0, 20, 40, 60, 80, 100, 120, 140, 160 and 165 minutes
Change From Baseline in Maximum Ambient Glucose Concentration (Gmax) After a Single Dose of OXM
Participants received on Day (-1) an overnight IV infusion of insulin titrated to achieve baseline fasting plasma glucose on Day 1 of between 90 and 130 mg/dL. Participants also received on Day (-1) a single dose of Lg or placebo for Lg, after which insulin infusion was discontinued. Following overnight fast, participants received on Day 1 OXM or placebo for OXM, accompanied by up to 160 minutes of GGI. During GGI glucose (20% D/W) was gradually infused at rates of 2,4,6 and 10 mg/kg/min, with each rate lasting approximately 40 minutes. Glucose levels were measured from blood collected at baseline and during GGI to determine the maximum ambient glucose concentration above baseline.
Measured: Baseline and up to 160 minutes after start of GGI
Change From Baseline in Beta Cell Sensitivity to Glucose (Φ) After a Single Dose of OXM
Beta cell sensitivity measures the ability to mount an insulin secretory response relative to the level of ambient plasma glucose. Participants received on Day (-1) an overnight IV infusion of insulin titrated to achieve baseline fasting plasma glucose on Day 1 of between 90 and 130 mg/dL. Participants also received on Day (-1) a single dose of Lg or placebo for Lg, after which insulin infusion was discontinued. Following overnight fast, participants received on Day 1 a single dose of OXM or placebo for OXM, accompanied by up to 160 minutes of GGI. During GGI glucose (20% D/W) was gradually infused at rates of 2,4,6 and 10 mg/kg/min, with each rate lasting 40 minutes. Glucose (G), insulin and C-peptide levels were measured from blood collected at baseline and during GGI, with the decay in C-peptide concentration used to indirectly estimate the Insulin Secretion Rate (ISR). Beta Cell Sensitivity (Φ) was determined from the regression of the ISR on ambient plasma glucose (G).
Measured: Baseline and up to160 minutes after start of GGI

Secondary outcomes (3)

Change From Baseline in Insulinotrophic Effect (ISR/G) at the Highest Glucose Infusion Rate After Two Periods of Placebo Treatment
The reproducibility of insulinotrophic effects was compared after two separate placebo treatment periods within the same treatment sequence. Participants received on Day (-1) an overnight IV infusion of insulin titrated to achieve baseline fasting plasma glucose on Day 1 of between 90 and 130 mg/dL. Participants also received on Day (-1) a single subcutaneous dose of placebo for Lg, after which insulin infusion was discontinued. Following overnight fast, participants received on Day 1 placebo for OXM, accompanied by up to 160 minutes of GGI. During GGI glucose (20% D/W) was gradually infused at rates of 2,4,6 and 10 mg/kg/min, with each rate lasting approximately 40 minutes. Over these two treatment periods glucose (G), insulin and C-peptide levels were measured from blood collected at the highest glucose infusion rate; with the decay in C-peptide concentration used to indirectly estimate the Insulin Secretion Rate (ISR), and hence to determine the insulinotrophic effect, ISR/G.
Measured: Baseline and 160 minutes after start of GGI at each placebo treatment period
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
Participants received on Day (-1) an overnight IV infusion of insulin titrated to achieve baseline fasting plasma glucose on Day 1 of between 90 and 130 mg/dL. Participants also received on Day (-1) a single dose of Lg or placebo for Lg, after which insulin infusion was discontinued. Following overnight fast, participants received on Day 1 a single dose of OXM or placebo for OXM, accompanied by up to 160 minutes of GGI. During GGI glucose (20% D/W) was gradually infused at rates of 2,4,6 and 10 mg/kg/min, with each rate lasting approximately 40 minutes. Glucose levels were measured from blood collected at baseline and during GGI to determine the maximum ambient glucose concentration above baseline.
Measured: Baseline and up to 160 minutes after start of GGI
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
Participants received on Day (-1) an overnight IV infusion of insulin titrated to achieve baseline fasting plasma glucose on Day 1 of between 90 and 130 mg/dL. Participants also received on Day (-1) a single dose of Lg or placebo for Lg, after which insulin infusion was discontinued. Following overnight fast, participants received on Day 1 a single dose of OXM or placebo for OXM, accompanied by up to 160 minutes of GGI. During GGI glucose (20% D/W) was gradually infused at rates of 2,4,6 and 10 mg/kg/min, with each rate lasting approximately 40 minutes. Glucose (G), insulin and C-peptide levels were measured from blood collected at baseline and during GGI; with the decay in C-peptide concentration used to indirectly estimate the Insulin Secretion Rate (ISR) and hence determine ISR/G.
Measured: Baseline and up to 160 minutes after start of GGI

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2011Jul 2011

First posted15 Jun 2011 (estimated)
Study startJun 2011
Primary completionJul 2011
Study completionJul 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01373450
Sponsor's protocol ID: 0000-222
Status last verified: Sep 2015
First submitted: 13 Jun 2011
Last updated: 2 Sep 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 29545266
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.
PubMed 27072496

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Evaluation of the Glucoregulatory Effects of GLP-1 Receptor Activation in Patients With Type 2 Diabetes Mellitus
ClinicalTrials.gov ID: NCT01373450
Acronym / sponsor ID: 0000-222
Conditions: Type 2 Diabetes Mellitus
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: Jun 2011
Primary completion: Jul 2011 (actual)
Study completion: Jul 2011 (actual)
First posted: 15 Jun 2011 (estimated)
Results: Posted 8 Jul 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 6

Arm	Type	Receives
OXM → Lg-0.6 → Pbo → Lg-1.2	Experimental	Drug: Oxyntomodulin, Drug: Liraglutide 0.6 mg, Drug: Placebo for Oxyntomodulin, Drug: Placebo for LiraglutideParticipants 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
Lg-0.6 → Pbo → OXM → Pbo	Experimental	Drug: Oxyntomodulin, Drug: Liraglutide 0.6 mg, Drug: Placebo for Oxyntomodulin, Drug: Placebo for LiraglutideParticipants 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
Pbo → OXM → Lg-0.6 → Pbo	Experimental	Drug: Oxyntomodulin, Drug: Liraglutide 0.6 mg, Drug: Placebo for Oxyntomodulin, Drug: Placebo for LiraglutideParticipants 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
Lg-0.6 → OXM → Pbo → Lg-1.2	Experimental	Drug: Oxyntomodulin, Drug: Liraglutide 0.6 mg, Drug: Liraglutide 1.2 mg, Drug: Placebo for Oxyntomodulin, Drug: Placebo for LiraglutideParticipants 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
OXM → Pbo → Lg-0.6 → Pbo	Experimental	Drug: Oxyntomodulin, Drug: Liraglutide 0.6 mg, Drug: Placebo for Oxyntomodulin, Drug: Placebo for LiraglutideParticipants 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
Pbo → Lg-0.6 → OXM → Lg-1.2	Experimental	Drug: Oxyntomodulin, Drug: Liraglutide 0.6 mg, Drug: Liraglutide 1.2 mg, Drug: Placebo for Oxyntomodulin, Drug: Placebo for LiraglutideParticipants 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

Who may qualify

Ages: 18 to 64 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (11 listed)

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®

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Oxyntomodulin3.0 pmol/kg/min as an intravenous (IV) infusion in the morning of the day of graded glucose infusion (GGI) (Day 1)	Drug	Lg-0.6 → OXM → Pbo → Lg-1.2, Lg-0.6 → Pbo → OXM → Pbo, OXM → Lg-0.6 → Pbo → Lg-1.2, OXM → Pbo → Lg-0.6 → Pbo, Pbo → Lg-0.6 → OXM → Lg-1.2, Pbo → OXM → Lg-0.6 → Pbo
Liraglutide 0.6 mgAlso: Victoza®Single subcutaneous dose in the evening of the day before the GGI (Day-1)	Drug	Lg-0.6 → OXM → Pbo → Lg-1.2, Lg-0.6 → Pbo → OXM → Pbo, OXM → Lg-0.6 → Pbo → Lg-1.2, OXM → Pbo → Lg-0.6 → Pbo, Pbo → Lg-0.6 → OXM → Lg-1.2, Pbo → OXM → Lg-0.6 → Pbo
Liraglutide 1.2 mgAlso: Victoza®Single subcutaneous dose in the evening of the day before the GGI (Day-1)	Drug	Lg-0.6 → OXM → Pbo → Lg-1.2, Pbo → Lg-0.6 → OXM → Lg-1.2
Placebo for OxyntomodulinIV infusion in the morning of the day of GGI (Day 1)	Drug	Lg-0.6 → OXM → Pbo → Lg-1.2, Lg-0.6 → Pbo → OXM → Pbo, OXM → Lg-0.6 → Pbo → Lg-1.2, OXM → Pbo → Lg-0.6 → Pbo, Pbo → Lg-0.6 → OXM → Lg-1.2, Pbo → OXM → Lg-0.6 → Pbo
Placebo for LiraglutideSingle subcutaneous dose in the evening of the day before the GGI (Day-1)	Drug	Lg-0.6 → OXM → Pbo → Lg-1.2, Lg-0.6 → Pbo → OXM → Pbo, OXM → Lg-0.6 → Pbo → Lg-1.2, OXM → Pbo → Lg-0.6 → Pbo, Pbo → Lg-0.6 → OXM → Lg-1.2, Pbo → OXM → Lg-0.6 → Pbo

Primary outcome

Change From Baseline in Time-weighted Average of Glucose Measured by Area Under the Curve (AUC) After a Single Dose of Oxyntomodulin (OXM)
Time frame: Baseline and during GGI at time points 0, 20, 40, 60, 80, 100, 120, 140, 160 and 165 minutes
Participants received on Day (-1) an overnight intravenous (IV) infusion of insulin titrated to achieve baseline fasting plasma glucose on Day 1 of between 90 and 130 mg/dL. Participants also received on Day (-1) a single dose of liraglutide (Lg) or placebo for Lg, after which insulin infusion was discontinued. Following overnight fast, participants received on Day 1 OXM or placebo for OXM, accompanied by up to 160 minutes of graded glucose infusion (GGI). During GGI glucose (20% D/W) was gradually infused at rates of 2,4,6 and 10 mg/kg/min, with each rate lasting approximately 40 minutes. Glucose levels were measured from blood collected at baseline and during GGI at the following minutes: 0, 20, 40, 60, 80, 100, 120, 140, 160 and 165 in order to calculate the time-weighted average change from baseline in glucose AUC from 0-160 minutes.
Change From Baseline in Maximum Ambient Glucose Concentration (Gmax) After a Single Dose of OXM
Time frame: Baseline and up to 160 minutes after start of GGI
Participants received on Day (-1) an overnight IV infusion of insulin titrated to achieve baseline fasting plasma glucose on Day 1 of between 90 and 130 mg/dL. Participants also received on Day (-1) a single dose of Lg or placebo for Lg, after which insulin infusion was discontinued. Following overnight fast, participants received on Day 1 OXM or placebo for OXM, accompanied by up to 160 minutes of GGI. During GGI glucose (20% D/W) was gradually infused at rates of 2,4,6 and 10 mg/kg/min, with each rate lasting approximately 40 minutes. Glucose levels were measured from blood collected at baseline and during GGI to determine the maximum ambient glucose concentration above baseline.
Change From Baseline in Beta Cell Sensitivity to Glucose (Φ) After a Single Dose of OXM
Time frame: Baseline and up to160 minutes after start of GGI
Beta cell sensitivity measures the ability to mount an insulin secretory response relative to the level of ambient plasma glucose. Participants received on Day (-1) an overnight IV infusion of insulin titrated to achieve baseline fasting plasma glucose on Day 1 of between 90 and 130 mg/dL. Participants also received on Day (-1) a single dose of Lg or placebo for Lg, after which insulin infusion was discontinued. Following overnight fast, participants received on Day 1 a single dose of OXM or placebo for OXM, accompanied by up to 160 minutes of GGI. During GGI glucose (20% D/W) was gradually infused at rates of 2,4,6 and 10 mg/kg/min, with each rate lasting 40 minutes. Glucose (G), insulin and C-peptide levels were measured from blood collected at baseline and during GGI, with the decay in C-peptide concentration used to indirectly estimate the Insulin Secretion Rate (ISR). Beta Cell Sensitivity (Φ) was determined from the regression of the ISR on ambient plasma glucose (G).

3 secondary outcomes

Change From Baseline in Insulinotrophic Effect (ISR/G) at the Highest Glucose Infusion Rate After Two Periods of Placebo Treatment
Time frame: Baseline and 160 minutes after start of GGI at each placebo treatment period
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
Time frame: Baseline and up to 160 minutes after start of GGI
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
Time frame: Baseline and up to 160 minutes after start of GGI

Results and safety

Results posted to the registry on 8 Jul 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
OXM --> Lg-0.6--> Pbo--> Lg-1.2	2	2
Lg-0.6 mg--> Pbo--> OXM--> Pbo	2	2
Pbo--> OXM--> Lg-0.6-->Pbo	2	2
Lg-0.6--> OXM--> Pbo--> Lg-1.2	2	2
OXM--> Pbo--> Lg-0.6--> Pbo	2	2
Pbo--> Lg-0.6--> OXM--> Lg-1.2	2	2

Primary outcome: Change From Baseline in Time-weighted Average of Glucose Measured by Area Under the Curve (AUC) After a Single Dose of Oxyntomodulin (OXM)

Time frame: Baseline and during GGI at time points 0, 20, 40, 60, 80, 100, 120, 140, 160 and 165 minutes. Least squares mean (Standard Deviation). Unit: mg/dL

Measure	Oxyntomodulin n = 12	Placebo n = 18
Value	106.3 (23.03)	122.6 (35.29)

Oxyntomodulin vs Placebo: Geometric Mean Ratio: 0.87 (90% CI 0.77 to 0.98), p = 0.024, t-test, 1 sided

Population analysed: Participants treated with Oxyntomodulin or placebo. Six participants were treated for two periods with placebo, resulting in placebo n = 18. Participants treated with Liraglutide were not analyzed for this outcome measure.

Primary outcome: Change From Baseline in Maximum Ambient Glucose Concentration (Gmax) After a Single Dose of OXM

Time frame: Baseline and up to 160 minutes after start of GGI. Least squares mean (Standard Deviation). Unit: mg/dL

Measure	Oxyntomodulin n = 12	Placebo n = 18
Value	211.0 (63.00)	272.9 (50.05)

Oxyntomodulin vs Placebo: Geometric Mean Ratio: 0.77 (90% CI 0.66 to 0.90), p = 0.004, t-test, 1 sided

Primary outcome: Change From Baseline in Beta Cell Sensitivity to Glucose (Φ) After a Single Dose of OXM

Time frame: Baseline and up to160 minutes after start of GGI. Least squares mean (Standard Deviation). Unit: ISR (ng/mL) / Glucose (mg/dL)

Measure	Oxyntomodulin n = 12	Placebo n = 18
Value	0.019 (0.010)	0.006 (0.003)

Oxyntomodulin vs Placebo: Least Square Mean Difference: 0.014 (90% CI 0.008 to 0.019), p <0.001, t-test, 1 sided

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 14 days after last dose of study medication. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Oxyntomodulin	0 of 12 (0%)	6 of 12 (50%)	Not reported
Liraglutide 0.6 mg	0 of 12 (0%)	7 of 12 (58.3%)	Not reported
Liraglutide 1.2 mg	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
Placebo	0 of 12 (0%)	8 of 12 (66.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29545266Shankar 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.
Derived from this study: PubMed 27072496Shankar 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Oxyntomodulin, Liraglutide 0.6 mg and Liraglutide 1.2 mg in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Time-weighted Average of Glucose Measured by Area Under the Curve (AUC) After a Single Dose of Oxyntomodulin (OXM) (time frame: Baseline and during GGI at time points 0, 20, 40, 60, 80, 100, 120, 140, 160 and 165 minutes). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01373450, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2015.