Effect of Different Fixed Pramlintide:Insulin Dose Ratios on Postprandial Glucose in T1DM

Study Overview
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Brief Summary
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To examine the effects of different fixed pramlintide:insulin dose ratios in subjects with type 1 diabetes on postprandial plasma glucose concentrations

Official Title
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A Phase 1, Randomized, Placebo-Controlled Single-Blind, Dose-Ranging, 4-Way Crossover Study to Evaluate the Effect of Different Fixed Pramlintide: Insulin Dose Ratios on Postprandial Glycemic Control in Subjects With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Pramlintide acetate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is 18 to 70 years old Is male, or is female and meets all the following criteria: Not breastfeeding Negative pregnancy test result and, if of childbearing potential, must practice and be willing to continue to practice appropriate birth control Has been diagnosed with type 1 diabetes mellitus for at least 1 year and not achieving glycemic goal while on MDI of insulin Has HbA1c between 7.0% and 9.0% Has been on MDI of regular insulin, at a dose not to exceed 10 units/breakfast for at least 3 months or has been on continuous subcutaneous insulin infusion (CSII), at a dose not to exceed 10 units/breakfast, for at least 3 months and is willing to switch to an MDI insulin regimen for 1 day prior to enrollment and through the study Has a body mass index (BMI) <30 kg/m2 Exclusion Criteria: Has experienced recurrent severe hypoglycemia requiring assistance within 6 months before Visit 1 Screening Has a history of hypoglycemia unawareness Has a confirmed diagnosis of gastroparesis Has been treated, is currently being treated, or is expected to require or undergo treatment with the following medications: Any antihyperglycemic agent other than insulin Drugs that directly affect gastrointestinal motility (e.g., anticholinergic agents such as atropine) Drugs that slow the intestinal absorption of nutrients (e.g., α-glucosidase inhibitors. Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the investigator, including but not limited to the following conditions: Hepatic disease Renal disease Gastrointestinal disease Pulmonary disease Organ transplantation Chronic infection (e.g., tuberculosis, human immunodeficiency virus, hepatitis B virus, or hepatitis C virus) Is currently treated or has been previously treated with SYMLIN/pramlintide or has participated in a SYMLIN/pramlintide clinical study within 3 months of Visit 1 (Screening). Has any clinically significant laboratory findings or medical history that may affect successful completion of the study and/or personal well-being Has donated blood within 2 months or is planning to donate blood during the study. Has had a major surgery or a blood transfusion within 2 months Has received any investigational drug within 1 month Has known allergies or hypersensitivity to any component of study treatment. Is an immediate family member of personnel directly affiliated with the study at the clinical study site, or is directly affiliated with the study at the clinical study site. Is employed by Amylin Pharmaceuticals, Inc (Amylin) (that is an employee, temporary contract worker, or designee responsible for the conduct of the study).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pramlintide 6 mcg per unit of insulin dose<br>The pramlintide dose will be calculated based on the subjects' individual insulin units. Dose ratio to be examined is pramlintide 6 mcg for each unit of insulin. | Drug: Pramlintide acetate<br> <br> |
| Experimental: Pramlintide 9 mcg per unit of insulin dose<br>The pramlintide dose will be calculated based on the subjects' individual insulin units. Dose ratio to be examined is pramlintide 9 mcg for each unit of insulin. | Drug: Pramlintide acetate<br> <br> |
| Experimental: Pramlintide 12 mcg per unit of insulin dose<br>The pramlintide dose will be calculated based on the subjects' individual insulin units. Dose ratio to be examined is pramlintide 12 mcg for each unit of insulin. | Drug: Pramlintide acetate<br> <br> |
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo Comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incremental area under the concentration-time curve (AUC(0-3 h)) of plasma glucose concentrations for each treatment |  | AUC 0-3 hrs compared to Placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incremental AUC (0-3 h) of plasma glucagon |  | 0-3 hrs compared to Placebo | 
| Absolute AUC (0-3 h), peak plasma concentration (Cmax), Cave, and Tmax of glucagon of plasma glucose. |  | 0-3 hrs compared to Placebo | 
| PK of pramlintide |  | 0-3 hrs compared to Placebo | 
| Safety |  | 0-3 hrs compared to Placebo | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pramlintide,, insulin,, type 1 diabetes,, reduction in postprandial glucose,, pramlintide:insulin dose-ratio