Safety, Tolerability and Pharmacokinetics of Liraglutide-depot in Healthy Subjects

Investigation on Safety, Tolerability and Pharmacokinetics of Liraglutide-depot in Healthy Subjects. A Randomised, Double-blind, Placebo-controlled Trial Investigating Subcutaneously Single Dose Escalation of a Sustained Release Formulation of Liraglutide Lysine in Healthy Male Subjects

This trial is conducted in the United States of America (USA). The aim of this trial is to investigate the safety, tolerability and pharmacokinetics (exposure in the body) of liraglutide-depot in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy; Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: liraglutide-depot; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Evansville, Indiana, United States, 47710
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Body mass index (BMI) between 20 and 35 kg/m^2 (both inclusive) with a body weight of at least 60 kg
• Apart from being obese (BMI above 30 kg/m^2) the subject has to be considered generally healthy

Exclusion Criteria:

• Medical history of, or presence of, cancer, diabetes or any clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrine, haematological, dermatological, venereal, neurological, psychiatric diseases or other major disorders
• Clinical or laboratory findings which suggest that the subject cannot be considered generally healthy
• Prescription medicine and non-prescription medicine with few exceptions
• Current and prior history of alcohol or drug abuse
• Current smoking of more than 5 cigarettes per day
• Mental incapacity, language barriers, or unwillingness to comply with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: placebo; Subjects will be randomised to receive a single dose of liraglutide-depot placebo, at increasing dose levels, injected s.c./subcutaneously (under the skin).
EXPERIMENTAL: Cohort 1a: Lira-depot 2.25 mg	Drug: liraglutide-depot; Subjects will be randomised to receive a single dose of liraglutide-depot, at increasing dose levels, injected s.c./subcutaneously (under the skin). Progression to next dose level (max. 8) will be based on safety evaluation.
EXPERIMENTAL: Cohort 2a: Lira-depot 6.75 mg	Drug: liraglutide-depot; Subjects will be randomised to receive a single dose of liraglutide-depot, at increasing dose levels, injected s.c./subcutaneously (under the skin). Progression to next dose level (max. 8) will be based on safety evaluation.
EXPERIMENTAL: Cohort 3a: Lira-depot 15 mg	Drug: liraglutide-depot; Subjects will be randomised to receive a single dose of liraglutide-depot, at increasing dose levels, injected s.c./subcutaneously (under the skin). Progression to next dose level (max. 8) will be based on safety evaluation.
EXPERIMENTAL: Cohort 4a: Lira-depot 30 mg	Drug: liraglutide-depot; Subjects will be randomised to receive a single dose of liraglutide-depot, at increasing dose levels, injected s.c./subcutaneously (under the skin). Progression to next dose level (max. 8) will be based on safety evaluation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment Emergent Adverse Events (TEAEs)	TEAEs: AEs from 1st exposure (exp) until follow-up (FU) or AEs with onset before 1st exp increasing in severity up to the FU. Mild AEs: no or transient symptoms, no interference (inf) with subject's daily activities. Moderate AEs: marked symptoms, moderate inf with subject's daily activities. Severe AEs: considerable inf with subject's daily activities, unacceptable. Serious AE: AE that at any dose results in death/ a life-threatening experience/ in-subject hospitalization/prolongation of existing hospitalisation; or persistent/significant disability/incapacity/congenital anomaly/birth defect.	Day 0 and up to 21 days after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Plasma Concentration of Liraglutide After a Single Dose of Liraglutide-depot	Day 0 through day 21 at 1,3,6,12,18, 24, 36, 48, 72, 96, 120, 168, 336, 504 hours post dose
Time to Maximum Plasma Concentration of Liraglutide After a Single Dose of Liraglutide-depot	Day 0 through day 21 at 1,3,6,12,18, 24, 36, 48, 72, 96, 120, 168, 336, 504 hours post dose
Area Under the Plasma Concentration Curve in the Period From the Time of Liraglutide-depot Administration to Infinity	Day 0 through day 21 at 1,3,6,12,18, 24, 36, 48, 72, 96, 120, 168, 336, 504 hours post dose
Area Under the Liraglutide Plasma Concentration Curve in the First Week Following Liraglutide-depot Administration for Subjects Without Liraglutide 6 mg/ml Pre-treatment	1,3,6,12,18, 24, 36, 48, 72, 96, 120, 168 hours post dose
Area Under the Plasma Concentration Curve in the First Week Following Liraglutide-depot Administration for Subjects With Liraglutide 6 mg/ml Pre-treatment	0 to 168 hours after dosing
Number of Subjects With Antibodies (Positive) or Without Antibodies (Negative) Against Liraglutide Observed at Pre-dose and at Last Follow-up	Day 0 and Day 21

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): March 1, 2012
• Study Completion (ACTUAL): March 1, 2012

Study Registration Dates

• First Submitted: November 2, 2011
• First Submitted That Met QC Criteria: November 14, 2011
• First Posted (ESTIMATE): November 17, 2011

Study Record Updates

• Last Update Posted (ACTUAL): March 23, 2017
• Last Update Submitted That Met QC Criteria: March 22, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: NN9223-3928; U1111-1123-0547 (OTHER: WHO)