Safety and Efficacy of BC LisPram

A Randomized Controlled Pilot Study to Assess the Pharmacokinetics, Pharmacodynamics, and Closed-loop Efficacy of BC LisPram Compared to Rapid Insulin in Pump-treated Adults With Type 1 Diabetes

This pilot study is a 50-hour randomized, open-label, crossover study in an inpatient setting assessing the safety, pharmacodynamics, pharmacokinetics, and closed-loop efficacy of i) BC LisPram delivery and ii) rapid insulin delivery.

Study Overview

• Status: Recruiting
• Conditions: Type1 Diabetes Mellitus
• Intervention / Treatment: Drug: 50-Hour Intervention - Rapid Insulin lispro; Drug: 50-Hour Intervention - BC LisPram

Detailed Description

Subjects will be randomized to intervention sequences. The first 6 participants will be randomly allocated to a sequence of three treatments composed of (i) treatment with active comparator insulin lispro, (ii) treatment with BC LisPram, and (iii) treatment with BC LisPram (dual wave bolus). The following 10 participants will be randomly allocated to a sequence of either two or three treatments. Each treatment period will last 50 hours. PK/PD assessment will be performed under an open-loop system and will be followed by a 24 hour of closed-loop assessment.

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Alexia Macina; Phone Number: +1 514-623-2520; Email: alexia.macina@affiliate.mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A3T2
      • Recruiting
      • Hygea Medical Clinic
      • Contact: Louise Ullyatt; Phone Number: 5149380995; Email: louise@cmhygea.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females ≥ 18 years of age.
• Clinical diagnosis of type 1 diabetes for at least 12 months. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.
• Insulin pump therapy for at least 3 months, with daily insulin needs ranging between 30 and 80 U.
• Most recent HbA1c ≤ 9.5% (over the last two months).
• Effective birth control in female participants of childbearing potential. Medically acceptable contraception methods include condom, pills, and intrauterine device.

Exclusion Criteria:

• Current or ≤ 1 month use of other antihyperglycemic agents (SGLT2, GLP-1, Metformin, Acarbose, etc....).
• Current use of glucocorticoid medication.
• Use of medication that alters gastrointestinal motility.
• Planned or ongoing pregnancy.
• Breastfeeding individuals
• Severe hypoglycemic episode within one month of admission.
• Severe diabetic ketoacidosis episode within one month of admission.
• Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
• Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
• Known hypersensitivity to any of the study drugs or their excipients.
• Allergy to paracetamol (acetaminophen).
• Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
• Clinically abnormal significant values for haemato, biochemistry, or urinalysis screening test as judged by the Principle Investigator for underlying disease.
• Failure to comply with team's recommendations (e.g. not willing to eat meals/snacks, not willing to change pump parameters, etc.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Rapid Insulin lispro - Conventional bolus; Participants will use subcutaneously-delivered rapid insulin (lispro) through pump therapy.	Drug: 50-Hour Intervention - Rapid Insulin lispro; Subcutaneous-delivery of insulin lispro using pump therapy.
EXPERIMENTAL: BC LisPram - Conventional bolus; Participants will use subcutaneously-delivered BC LisPram through pump therapy.	Drug: 50-Hour Intervention - BC LisPram; Subcutaneous-delivery of BC LisPram using pump therapy.
EXPERIMENTAL: BC LisPram - Dual wave bolus; Participants will use subcutaneously-delivered BC LisPram through pump therapy. During dual wave bolusing, 50% of the prandial bolus is delivered immediately, and the other 50% delivered over the next 30 minutes.	Drug: 50-Hour Intervention - BC LisPram; Subcutaneous-delivery of BC LisPram using pump therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of Pramlintide	Area under the pramlintide concentration-time curve	Breakfast, lunch, dinner from 0 to 4 hours
Pharmacokinetics of Insulin	Area under the insulin concentration-time curve	Breakfast, lunch, dinner from 0 to 4 hours
Pharmacokinetics of Paracetamol	Area under the paracetamol concentration-time curve	Breakfast and dinner from 0 to 4 hours
Glucose Pharmacodynamics	Area under the sensor glucose concentration-time curve	Breakfast, lunch and dinner from 0 to 4 hours
Glucagon Pharmacodynamics	Area under the plasma glucagon concentration-time curve	Breakfast and dinner from 0 to 4 hours
Hypoglycaemic episodes	Number of hypoglycaemic episodes during the 0 to 50 hour period.	0 to 50 hours
Gastrointestinal symptoms	Frequency of gastrointestinal symptoms during the 0 to 50 hour period.	0 to 50 hours
Local tolerability at pump injection site	Local tolerability at pump injection site during the 0 to 50 hour period.	0 to 50 hours
Incidence of adverse event	Number of adverse events during the 0 to 50 hour period.	0 to 50 hours

Collaborators and Investigators

• Sponsor: Michael Tsoukas
• Collaborators: Adocia
• Investigators: Principal Investigator: Michael Tsoukas, MD, Applied Medical Informatics Research Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 28, 2021
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): June 1, 2022

Study Registration Dates

• First Submitted: July 15, 2021
• First Submitted That Met QC Criteria: July 21, 2021
• First Posted (ACTUAL): July 22, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 16, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Pramlintide
• 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
• Other Study ID Numbers: 2021-00050920; Pro00050920 (OTHER: Research Ethics Board - Advarra)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No