Safety and Efficacy of BC LisPram

Phase 1

• Conditions: Type1 Diabetes Mellitus
• Interventions: Drug: 50-Hour Intervention - Rapid Insulin lispro; Drug: 50-Hour Intervention - BC LisPram

• Registration Number: NCT04972175
• Lead Sponsor: Michael Tsoukas

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-07-15
• Study First Submitted QC: 2021-07-21
• Study First Posted: 2021-07-22
• Study Start: 2021-07-28
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-14
• Last Update Posted: 2022-02-16
• Primary Completion: 2022-06
• Study Completion: 2022-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 16

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Rapid Insulin lispro - Conventional bolus	50-Hour Intervention - Rapid Insulin lispro	Participants will use subcutaneously-delivered rapid insulin (lispro) through pump therapy.
BC LisPram - Conventional bolus	50-Hour Intervention - BC LisPram	Participants will use subcutaneously-delivered BC LisPram through pump therapy.
BC LisPram - Dual wave bolus	50-Hour Intervention - BC LisPram	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.

Primary Outcome Measures

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

Trial Locations

Locations (1)

Hygea Medical Clinic; 🇨🇦 Montreal, Quebec, Canada