Trial Outcomes & Findings for Evaluate the Immunogenicity of a Novel Glucagon Formulation (NCT NCT01959334)

NCT ID: NCT01959334

Last Updated: 2019-09-06

Results Overview

Glucagon anti-drug antibodies (ADA) were assessed at baseline through study completion. Percentage of participants (Pts) with ADA=(number of Pts with treatment-emergent ADA/number of Pts assessed)\*100. Treatment-Emergent ADA includes treatment-induced ADA and treatment boosted ADA. Treatment-induced is defined as participants with 'Not Detected' ADA at baseline (drug-naive) and at least one post-baseline ADA 'Detected' sample with a corresponding titer that is one 2-fold dilution higher than the MRD (minimal required dilution) of the assay. For the nasal glucagon Tier 1-3 ADA screening assay, the MRD is 1:20. Treatment-boosted is defined as Patient with ADA 'Detected' at baseline (drug-naive) and at least one post-baseline ADA 'Detected' sample with a corresponding titer that is at least (\>or=) 4-fold higher than the baseline titer.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

75 participants

Primary outcome timeframe

Baseline through study completion (up to 10 weeks)

Results posted on

2019-09-06

Participant Flow

Participant milestones

Participant milestones
Measure	Glucagon IM Glucagon dose of 1 milligram (mg) administered intramuscularly as 3 doses separated by at least 7 days.	Nasal Glucagon (NG) NG administered at 3 mg as 3 doses, separated by at least 7 days.
First Dose STARTED	26	49
First Dose COMPLETED	26	49
First Dose NOT COMPLETED	0	0
Second Dose STARTED	26	49
Second Dose COMPLETED	25	49
Second Dose NOT COMPLETED	1	0
Third Dose STARTED	25	49
Third Dose COMPLETED	25	48
Third Dose NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Glucagon IM Glucagon dose of 1 milligram (mg) administered intramuscularly as 3 doses separated by at least 7 days.	Nasal Glucagon (NG) NG administered at 3 mg as 3 doses, separated by at least 7 days.
Second Dose Adverse Event	1	0
Third Dose Adverse Event	0	1

Baseline Characteristics

Evaluate the Immunogenicity of a Novel Glucagon Formulation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glucagon IM n=26 Participants Glucagon dose of 1 mg administered intramuscularly as 3 doses separated by at least 7 days.	Nasal Glucagon (NG) n=49 Participants NG administered at 3 mg as 3 doses, separated by at least 7 days.	Total n=75 Participants Total of all reporting groups
Age, Continuous	42 years STANDARD_DEVIATION 12 • n=93 Participants	43 years STANDARD_DEVIATION 15 • n=4 Participants	43 years STANDARD_DEVIATION 14 • n=27 Participants
Sex: Female, Male Female	6 Participants n=93 Participants	13 Participants n=4 Participants	19 Participants n=27 Participants
Sex: Female, Male Male	20 Participants n=93 Participants	36 Participants n=4 Participants	56 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) White	24 Participants n=93 Participants	44 Participants n=4 Participants	68 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment Canada	26 Participants n=93 Participants	49 Participants n=4 Participants	75 Participants n=27 Participants
BMI (Body Mass Index)	27.08 kilogram per square metre (kg/m2) STANDARD_DEVIATION 4.28 • n=93 Participants	27.18 kilogram per square metre (kg/m2) STANDARD_DEVIATION 3.93 • n=4 Participants	27.15 kilogram per square metre (kg/m2) STANDARD_DEVIATION 4.03 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline through study completion (up to 10 weeks)

Population: All enrolled participants who received at least 1 dose of study drug with an evaluable baseline ADA result and a post-baseline ADA result.

Outcome measures

Outcome measures
Measure	Glucagon IM n=26 Participants Glucagon dose of 1 mg administered intramuscularly as 3 doses separated by at least 7 days.	Nasal Glucagon (NG) n=49 Participants NG administered at 3 mg as 3 doses, separated by at least 7 days.
Percentage of Participants With Treatment-emergent Anti-Drug Antibody (ADA)	0 percentage of participants	2.0 percentage of participants

PRIMARY outcome

Timeframe: Baseline through study completion (up to 10 weeks)

Population: All enrolled participants who received at least 1 dose of study drug and either had baseline and at least 1 post-baseline evaluable samples or had no evaluable baseline and all negative post-baseline anti-drug antibody negative samples.

Outcome measures

Outcome measures
Measure	Glucagon IM n=26 Participants Glucagon dose of 1 mg administered intramuscularly as 3 doses separated by at least 7 days.	Nasal Glucagon (NG) n=49 Participants NG administered at 3 mg as 3 doses, separated by at least 7 days.
Percentage of Participants With Neutralizing Antibodies	0 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: First dose of study drug through the post-study completion (up to 10 weeks)

Population: Participants who received at least one dose of glucagon (IM or NG).

Safety parameters assessed included the occurrence of adverse events, the measurement of clinical laboratory parameters; vital signs, ECGs, physical examination, blood glucose, and examination of the injection site (following the IM administration). An AE was defined as any untoward medical occurrence in a clinical investigation subject administered the investigational product and which did not necessarily have a causal relationship with this treatment A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Outcome measures

Outcome measures
Measure	Glucagon IM n=26 Participants Glucagon dose of 1 mg administered intramuscularly as 3 doses separated by at least 7 days.	Nasal Glucagon (NG) n=49 Participants NG administered at 3 mg as 3 doses, separated by at least 7 days.
Number of Participants With At Least One Adverse Event	21 Participants	49 Participants

Adverse Events

Glucagon IM

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Nasal Glucagon (NG)

Serious events: 0 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee This study was conducted by a Contract Research Organization. The Sponsor is and shall remain owner of all data pertaining to and/or resulting from the Study as well as all rights on intellectual property and patents arising from the said Study. Confidential Information may not be disclosed to any third party without the other party's prior written consent (except to the relevant authorities, providing the confidentiality is maintained).
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Glucagon IM n=26 participants at risk Glucagon dose of 1 mg administered intramuscularly as 3 doses separated by at least 7 days.	Nasal Glucagon (NG) n=49 participants at risk NG administered at 3 mg as 3 doses, separated by at least 7 days.
Nervous system disorders Headache	11.5% 3/26 • Number of events 5 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	51.0% 25/49 • Number of events 38 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Nervous system disorders Somnolence	15.4% 4/26 • Number of events 4 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	12.2% 6/49 • Number of events 6 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Nervous system disorders Dizziness	11.5% 3/26 • Number of events 4 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	14.3% 7/49 • Number of events 10 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Nervous system disorders Dysgeusia	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	14.3% 7/49 • Number of events 12 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Nervous system disorders Parosmia	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	12.2% 6/49 • Number of events 6 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Nervous system disorders Tremor	11.5% 3/26 • Number of events 3 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	6.1% 3/49 • Number of events 3 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Nervous system disorders Sinus headache	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	4.1% 2/49 • Number of events 3 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Eye disorders Lacrimation increased	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	98.0% 48/49 • Number of events 154 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Eye disorders Ocular hyperaemia	3.8% 1/26 • Number of events 1 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	42.9% 21/49 • Number of events 30 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Eye disorders Eye pruritus	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	30.6% 15/49 • Number of events 19 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Eye disorders Eye irritation	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	6.1% 3/49 • Number of events 4 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Respiratory, thoracic and mediastinal disorders Nasal discomfort	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	40.8% 20/49 • Number of events 53 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	42.9% 21/49 • Number of events 67 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	40.8% 20/49 • Number of events 28 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	24.5% 12/49 • Number of events 17 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	14.3% 7/49 • Number of events 8 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	14.3% 7/49 • Number of events 8 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Respiratory, thoracic and mediastinal disorders Rhinalgia	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	8.2% 4/49 • Number of events 4 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
General disorders Injection site pain	23.1% 6/26 • Number of events 8 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	0.00% 0/49 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
General disorders Fatigue	11.5% 3/26 • Number of events 3 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	6.1% 3/49 • Number of events 3 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
General disorders Feeling hot	3.8% 1/26 • Number of events 1 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	8.2% 4/49 • Number of events 4 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
General disorders Injection site anaesthesia	11.5% 3/26 • Number of events 4 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	0.00% 0/49 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
General disorders Injection site reaction	11.5% 3/26 • Number of events 3 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	0.00% 0/49 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
General disorders Injection site discomfort	7.7% 2/26 • Number of events 2 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	0.00% 0/49 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Gastrointestinal disorders Nausea	11.5% 3/26 • Number of events 3 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	26.5% 13/49 • Number of events 30 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Gastrointestinal disorders Vomiting	7.7% 2/26 • Number of events 4 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	18.4% 9/49 • Number of events 22 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Vascular disorders Hot flush	11.5% 3/26 • Number of events 3 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	10.2% 5/49 • Number of events 6 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Metabolism and nutrition disorders Hypoglycemia	3.8% 1/26 • Number of events 1 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	6.1% 3/49 • Number of events 6 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	4.1% 2/49 • Number of events 3 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Blood and lymphatic system disorders Iron deficiency anaemia	3.8% 1/26 • Number of events 1 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	0.00% 0/49 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Ear and labyrinth disorders Ear pain	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	2.0% 1/49 • Number of events 3 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Ear and labyrinth disorders Ear pruritus	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	4.1% 2/49 • Number of events 2 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Eye disorders Eye Pain	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	4.1% 2/49 • Number of events 2 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Eye disorders Ocular discomfort	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	6.1% 3/49 • Number of events 3 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Gastrointestinal disorders Abdominal Discomfort	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	2.0% 1/49 • Number of events 1 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Gastrointestinal disorders Abdominal Distension	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	2.0% 1/49 • Number of events 1 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Gastrointestinal disorders Abdominal Pain	3.8% 1/26 • Number of events 1 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	0.00% 0/49 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Gastrointestinal disorders Abnormal faeces	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	2.0% 1/49 • Number of events 1 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Gastrointestinal disorders Dry mouth	3.8% 1/26 • Number of events 1 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	0.00% 0/49 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).
Gastrointestinal disorders Flatulence	0.00% 0/26 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).	2.0% 1/49 • Number of events 1 • The period of observation of adverse events extended from time of the first dose of study drug until the post-study completion (up to 10 weeks).