Pharmacokinetics of Ultra-Rapid-Acting Insulin Lispro (URAL) in Type 1 Diabetes Mellitus

A Randomised Trial Investigating Pharmacokinetic Properties of Ultra-Rapid-Acting Insulin Lispro (URAL) in Subjects With Type 1 Diabetes Mellitus

To compare the early pharmacokinetic exposure of URAL and insulin lispro (ILisp).

Study Overview

• Status: Withdrawn
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: URAL

Detailed Description

To compare the total pharmacodynamic response of URAL and insulin lispro.

To compare the total pharmacokinetic exposure between URAL and insulin lispro.

To assess the safety and tolerability of URAL and insulin lispro.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany
    • Profil Institut für Stoffwechselforschung GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Signed informed consent
2. Male subjects age 18-65 years inclusive
3. Type 1 diabetes mellitus diagnosed clinically >= 12 months
4. Treatment with multiple daily insulin injections or CSII >= 12 months
5. Current total daily insulin treatment <1.2 (I)U/kg/day
6. Current total daily bolus insulin treatment <0.7 (I)U/kg/day
7. Body mass index 18.0-30.0 kg/m2 inclusive
8. HbA1c =<9.0% by local laboratory analysis (one retest within a week is permitted with the result of the last test being conclusive)
9. C-peptide =< 0.30 nmol/L

Exclusion Criteria:

1. Known or suspected hypersensitivity to trial products or related products
2. Previous participation in this trial. .
3. Receipt of any non-marketed investigational product within 3 months
4. Clinically significant abnormal haematology, biochemistry, liver enzymes, or coagulation screening tests
5. Suffer from or history of a life threatening disease or any clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, haematological, dermatological, venereal , neurological, psychiatric diseases or other major disorders
6. History of deep leg vein thrombosis or a frequent appearance of deep leg vein thrombosis in 1st degree relatives
7. Cardiac problems defined as decompensated heart failure (New York Heart Association class III and IV) at any time and/or angina pectoris within the last 12 months and/or acute myocardial infarction at any time.
8. Supine blood pressure at screening outside the range of 90-140 mmHg for systolic or 50-90 mmHg for diastolic . Pulse outside 50 to 90 bpm.
9. Clinically significant abnormal ECG at screening.
10. Proliferative retinopathy or maculopathy and/or severe neuropathy, in particular autonomic neuropathy.
11. Any disease or condition that, in the opinion of the Investigator, would represent an unacceptable risk for the subject's safety.
12. Subject positive for HBs-Ag, HCV-Ab
13. Positive result to the screening test for HIV-1 antibodies, HIV-2 antibodies, or HIV-1 antigen according to locally used diagnostic testing.
14. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
15. Subject who has donated blood or plasma in the past month or more than 500 mL within 3 months.
16. Surgery or trauma with significant blood loss (more than 500 mL) within 3 months.
17. Current treatment with systemic (oral, IV, or inhaled) corticosteroids, monoamine oxidase inhibitors, NSAID, prostaglandin blockers, systemic non-selective beta-blockers, growth hormone (last 3 months), non-routine vitamins or herbal products (last 2 weeks). Thyroid hormones are not allowed unless the use of these has been stable during the last 3 months. Routine vitamins are permitted up to 48 hours prior to dosing.
18. Significant history of alcoholism and/or drug/chemical abuse as per Investigator's judgement or a positive result in the urine drug/alcohol breath test screen at the screening visit.
19. Heavy smoker
20. Not able or willing to refrain from smoking and use of nicotine.
21. Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemia event during the last 12 months) or hypoglycaemic unawareness.
22. Subject with mental incapacity or language barriers precluding adequate understanding.
23. Potentially non-compliant or uncooperative during the trial.
24. Any condition that would interfere with trial participation or evaluation of results.
25. No relevant lipodystrophy within the area of drug administration and Doppler sonography.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: URAL vs. Insulin lispro; Each subject will randomly be allocated to a treatment sequence consisting of 2 dosing visits during which the subject in a euglycaemic clamp setting will receive either a single dose of insulin lispro or URAL at predefined fixed dose levels in a randomized order.	Drug: URAL; Other Names: Ultra-Rapid-Acting Insulin Lispro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of URAL	Area under the serum insulin lispro concentration-time curve from 0-30 minutes after administration	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Onset of appearance of serum insulin lispro	Measurement of time to reach insulin lispro concentration >30 pmol/L in the serum	1 day
Number of subjects with adverse events	Assessment of safety and tolerability of URAL	1 day

Collaborators and Investigators

• Sponsor: Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc.
• Collaborators: Profil Institut für Stoffwechselforschung GmbH

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: July 30, 2014
• First Submitted That Met QC Criteria: July 30, 2014
• First Posted (Estimate): August 1, 2014

Study Record Updates

• Last Update Posted (Actual): July 15, 2020
• Last Update Submitted That Met QC Criteria: July 14, 2020
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: phase 1; diabetes mellitus; insulin lispro; male subjects
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Lispro; Insulin, Short-Acting
• Other Study ID Numbers: PER511