Clinical trial NCT02806960: A Study of Single and Repeated Doses of Glucagon Administered to Participants With Diabetes
Official title: A Single Center, Randomized, 4-Period Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of Single or Repeated 3 mg Doses of Intranasally Administered Glucagon in Adults With Type 1 or Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Locemia Solutions ULC
First posted: 2016-06-21
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This study will investigate how the body processes nasal glucagon and the effect of nasal glucagon on the body. After an 8-hour overnight fast and 4 hours after the start of a low-carbohydrate breakfast, the study drug will be delivered into the participant's nostril(s) (intranasally) once or twice in each of four study periods. The study is open to adults with type 1 or type 2 diabetes and is expected to last about 50 days for each participant.


Eligibility criteria: Inclusion Criteria:

* Males or females with a history of Type 1 or Type 2 insulin-using diabetes of at least 1 year duration (basal only, basal bolus, meal-time only, or twice a day pre-mixed insulin)
* A female participant must meet one of the following criteria:

  * Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens from at least 28 days prior to the first administration of the study drug, during the study and for at least 30 days after the last dose of the study drug.
  * Participant is of non-childbearing potential, defined as surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (at least 1 year without menses)
* Participants with a body mass index (BMI) greater than or equal to 18.50 kilograms per square meter (kg/m²) and below 35.00 kg/m²
* Light-, non- or ex-smokers
* In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the Investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations

Exclusion Criteria:

* Females who are pregnant, actively attempting to get pregnant, or are lactating
* History of significant hypersensitivity to glucagon or any related products as well as severe hypersensitivity reactions (such as angioedema) to any drugs
* Presence of significant gastrointestinal, liver or kidney disease, or any other conditions which in the judgment of the Investigator could interfere with the absorption, distribution, metabolism or excretion of drugs, or could potentiate or predispose to undesired effects
* Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
* Known presence of rare hereditary problems of galactose and /or lactose intolerance
* Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin secreting pancreas tumor) Presence of clinically significant findings on nasal examination or bilateral anterior rhinoscopy, such as structural abnormalities, nasal polyps, marked septal deviation, nasal tumors
* Nasal surgery in the previous 28 days before Day 1 of this study
* Daily use of a systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this study
* Any other concomitant maintenance therapy that would influence the outcome of the trial or compromise the safety of the participant, at the discretion of the Investigator and the Sponsor, in the previous 28 days before Day 1 of this study
* Significant history of drug dependency or alcohol abuse
* Any clinically significant illness in the previous 28 days before Day 1 of this study
* Any history of tuberculosis and/or prophylaxis for tuberculosis
* Positive urine screening of alcohol and/or drugs of abuse
* Concurrent participation or intention of participating in another clinical trial during this study
* Participants who took an Investigational Product (in another clinical trial) in the previous 28 days before Day 1 of this study or who have already participated in this clinical study
* Participants who donated 50 milliliters (mL) or more of blood in the previous 28 days before Day 1 of this study
* Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before Day 1 of this study

Primary outcomes:
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T (AUC[0-tlast]) of Baseline Adjusted Glucagon
timeFrame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment
measure: PK: Area Under the Curve Extrapolated to Infinity (AUC[0-inf]) of Baseline Adjusted Glucagon
timeFrame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment
measure: PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon
timeFrame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment
measure: PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon
timeFrame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment
measure: Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC₀-₁.₅) of Blood Glucose (BG)
timeFrame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, and 1.5 hours post dose for each treatment
measure: PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose
timeFrame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment
measure: PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax)
timeFrame: Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Mount-Royal
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Quebec
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: