Safety and Efficacy of BC LisPram

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Type1 Diabetes Mellitus

Intervention / Treatment
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* Drug: 50-Hour Intervention - Rapid Insulin lispro
* Drug: 50-Hour Intervention - BC LisPram


Participation Criteria
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Eligibility Criteria
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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.).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rapid Insulin lispro - Conventional bolus<br>Participants will use subcutaneously-delivered rapid insulin (lispro) through pump therapy. | Drug: 50-Hour Intervention - Rapid Insulin lispro<br>* Subcutaneous-delivery of insulin lispro using pump therapy.<br>|
| Experimental: BC LisPram - Conventional bolus<br>Participants will use subcutaneously-delivered BC LisPram through pump therapy. | Drug: 50-Hour Intervention - BC LisPram<br>* Subcutaneous-delivery of BC LisPram using pump therapy.<br>|
| Experimental: BC LisPram - Dual wave bolus<br>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<br>* Subcutaneous-delivery of BC LisPram using pump therapy.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pramlintide