Phase 2, Randomized, Open-Label, Crossover, PD/PK Study of a Novel Pram-Insulin Co-Formulation in Adults With T1D

Study Overview
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Brief Summary
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This is a randomized, open-label, active-controlled, single-dose, 3-treatment, 3-period, 3-way crossover, comparative PD and PK inpatient study in adults with T1D. The study comprises 5 visits: Screening (Visit 1), Treatment Periods (Visits 2 - 4), and Follow-Up (Visit 5).

Official Title
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A Phase 2, Single-Dose, Randomized, Open-Label, Active-Controlled, Crossover, Pharmacodynamic, and Pharmacokinetic Comparative Study of a Novel Pramlintide-Insulin Co-Formulation in Adults With Type 1 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 1, Insulin-dependent Diabetes Mellitus

Intervention / Treatment
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* Drug: PRAM9
* Drug: Regular Insulin + Pramlintide
* Drug: Regular Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understands the study procedures, alternative treatment available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent Male or non-pregnant, non-lactating female diagnosed with T1D for at least 24 months prior to Screening. Aged 18 to 64 years of age, inclusive On a stable insulin regimen for 21 days prior to Screening (no greater than ± 20% variability in total daily dose) Have a plasma C-peptide level < 0.6 ng/mL at Screening Have an HbA1c < 10% at Screening Body mass index (BMI) in the range of ≥ 18 to ≤ 35 kg/m2 at Screening For women of childbearing potential, there is a requirement for a negative urine pregnancy test at Screening and for agreement to use contraception throughout the study and for 7 days after the last dose of study drug. Acceptable contraception includes birth control pill/patch/vaginal ring, Depo-Provera® (medroxyprogesterone acetate), Norplant® System (levonorgestrel), an intra-uterine device (IUD), the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence. Fasting Serum triglyceride concentration < 200 mg/dL Exclusion Criteria: Currently being treated with pramlintide or has discontinued pramlintide within 21 days of Screening Currently using an insulin pump Has renal insufficiency (serum creatinine > 3.0 mg/dL) or end-stage renal disease requiring renal replacement therapy Has hepatic disease, including serum ALT or AST ≥ 3 times the upper limit of normal (ULN) Has hepatic synthetic insufficiency (serum albumin < 3.0 g/dL) Has hematocrit ≤ 30% Has hematocrit ≤ 30% Has out-of-range systolic or diastolic BP readings at Screening (systolic BP < 90 or > 150 mm Hg or diastolic BP < 50 or > 100 mm Hg) Has clinically significant ECG abnormalities at Screening Has congestive heart failure, NYHA Class III or IV Has history of myocardial infarction, unstable angina, or revascularization within 6 months prior to Screening Has history of a cerebrovascular accident in 6 months prior to Screening with major neurological deficits Has active malignancy within 5 years prior to Screening (exception: basal cell or squamous cell skin cancers) Has had major surgical operation within 60 days prior to Screening or planned surgical operation during the study Has a seizure disorder (other than with suspected or documented hypoglycemia) Has a current bleeding disorder, treatment with anticoagulants, or platelet count < 50 ×109/L Has a history of allergies or significant hypersensitivity to pramlintide or any pramlintide-related products or to any of the excipients in the investigational formulation Has a history of positive test result for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Has a concurrent illness not controlled by a stable therapeutic regimen Tests positive for drugs of abuse at Screening. Subjects testing positive for tetrahydrocannabinol (THC) at Screening or reporting active marijuana use will be allowed to participate in the study at the discretion of the investigator. Has active substance or alcohol abuse (> 21 drinks/week for males or > 14 drinks/week for females) Has participated in other studies involving administration of an investigational drug within 30 days or 5 half-lives prior to Screening (whichever is longer) or during participation in the current study There is any reason the investigator deems exclusionary Has donated blood within 8 weeks prior to Screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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 |
| --- | --- |
| Experimental: PRAM9<br>Xeris pramlintide + insulin co-formulation | Drug: PRAM9<br>* SC injection<br>Drug: Regular Insulin + Pramlintide<br>* Separate SC injections<br>Drug: Regular Insulin<br>* SC injection<br>|
| Experimental: Regular Insulin + Pramlintide<br>Humulin® + Symlin® pen as separate injections | Drug: PRAM9<br>* SC injection<br>Drug: Regular Insulin + Pramlintide<br>* Separate SC injections<br>Drug: Regular Insulin<br>* SC injection<br>|
| Active Comparator: Regular Insulin<br>Humulin® | Drug: PRAM9<br>* SC injection<br>Drug: Regular Insulin + Pramlintide<br>* Separate SC injections<br>Drug: Regular Insulin<br>* SC injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve 0-180 minutes |  | 0-180 minutes following administration of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose time above 180 mg/dL |  | 0-180 minutes following administration of study drug | 
| Glucose time in range |  | 0-180 minutes following administration of study drug | 
| Plasma glucose maximum concentration (Cmax) |  | 0-180 minutes following administration of study drug | 
| Plasma glucose time to maximum concentration (Tmax) |  | 0-180 minutes following administration of study drug |