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

NCT ID: NCT04074317

Last Updated: 2024-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-22
• Study Completion Date: 2020-04-02

Brief Summary

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).

Detailed Description

The primary objective of this study is to evaluate the PD properties of a single dose of PRAM9 compared to single doses of regular insulin and regular insulin plus pramlintide (co-administered as separate injections) in adults with T1D. The secondary objectives of this study are to evaluate the safety and PK profiles of a single dose of PRAM9 compared to single doses of regular insulin and regular insulin plus pramlintide (co-administered as separate injections) in adults with T1D. During each treatment period subjects will receive a single SC dose of PRAM9, regular insulin, or co-administered regular insulin plus pramlintide.

Conditions

Diabetes Mellitus, Type 1; Insulin-dependent Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PRAM9 to Regular Insulin to Regular Insulin+pramlintide

Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin (Humulin®) to Regular Insulin+pramlintide (Symlin® pen) as separate SC injections

Group Type: EXPERIMENTAL

PRAM9

Intervention Type: DRUG

SC injection

Regular Insulin + Pramlintide

Intervention Type: DRUG

Separate SC injections

Regular Insulin

Intervention Type: DRUG

SC injection

Regular Insulin to Regular Insulin+pramlintide to PRAM9

Regular Insulin (Humulin®) to Regular Insulin+pamlintide (Symlin® pen) as separate SC injections to PRAM9

Group Type: EXPERIMENTAL

PRAM9

Intervention Type: DRUG

SC injection

Regular Insulin + Pramlintide

Intervention Type: DRUG

Separate SC injections

Regular Insulin

Intervention Type: DRUG

SC injection

Regular Insulin+pramlintide to PRAM9 to Regular Insulin

Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin

Group Type: EXPERIMENTAL

PRAM9

Intervention Type: DRUG

SC injection

Regular Insulin + Pramlintide

Intervention Type: DRUG

Separate SC injections

Regular Insulin

Intervention Type: DRUG

SC injection

PRAM9 to Regular Insulin+pramlintide to Regular Insulin

Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Regular Insulin

Group Type: EXPERIMENTAL

PRAM9

Intervention Type: DRUG

SC injection

Regular Insulin + Pramlintide

Intervention Type: DRUG

Separate SC injections

Regular Insulin

Intervention Type: DRUG

SC injection

Regular Insulin to PRAM9 to Regular Insulin+pramlintide

Regular Insulin (Humulin®) to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin+pramlintide (Symlin® pen) as separate SC injections to Regular Insulin

Group Type: EXPERIMENTAL

PRAM9

Intervention Type: DRUG

SC injection

Regular Insulin + Pramlintide

Intervention Type: DRUG

Separate SC injections

Regular Insulin

Intervention Type: DRUG

SC injection

Regular Insulin+pramlintide to Regular Insulin to PRAM9

Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin to Xeris pramlintide + insulin co-formulation (PRAM9)

Group Type: EXPERIMENTAL

PRAM9

Intervention Type: DRUG

SC injection

Regular Insulin + Pramlintide

Intervention Type: DRUG

Separate SC injections

Regular Insulin

Intervention Type: DRUG

SC injection

Interventions

PRAM9

SC injection

Intervention Type: DRUG

Regular Insulin + Pramlintide

Separate SC injections

Intervention Type: DRUG

Regular Insulin

SC injection

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Understands the study procedures, alternative treatment available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent

2. Male or non-pregnant, non-lactating female diagnosed with T1D for at least 24 months prior to Screening.

3. Aged 18 to 64 years of age, inclusive

4. On a stable insulin regimen for 21 days prior to Screening (no greater than ± 20% variability in total daily dose)

5. Have a plasma C-peptide level < 0.6 ng/mL at Screening

6. Have an HbA1c < 10% at Screening

7. Body mass index (BMI) in the range of ≥ 18 to ≤ 35 kg/m2 at Screening

8. 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.

9. Fasting Serum triglyceride concentration < 200 mg/dL

Exclusion Criteria

1. Currently being treated with pramlintide or has discontinued pramlintide within 21 days of Screening

2. Currently using an insulin pump

3. Has renal insufficiency (serum creatinine <3.0 mg/dL) or end-stage renal disease requiring renal replacement therapy

4. Has hepatic disease, including serum ALT or AST ≥3 times the upper limit of normal (ULN)

5. Has hepatic synthetic insufficiency (serum albumin <3.0 g/dL)

6. Has a hematocrit value that is exclusionary: Female <35.5% and Male <38.3%

7. Has a hemoglobin value that is exclusionary: Female <11.5 g/dL and Male <12.5 g/dL

8. 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)

9. Has clinically significant ECG abnormalities at Screening

10. Has congestive heart failure, NYHA Class III or IV

11. Has history of myocardial infarction, unstable angina, or revascularization within 6 months prior to Screening

12. Has history of a cerebrovascular accident in 6 months prior to Screening with major neurological deficits

13. Has active malignancy within 5 years prior to Screening (exception: basal cell or squamous cell skin cancers)

14. Has had major surgical operation within 60 days prior to Screening or planned surgical operation during the study

15. Has a seizure disorder (other than with suspected or documented hypoglycemia)

16. Has a current bleeding disorder, treatment with anticoagulants, or platelet count <50 ×10^9/L

17. 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

18. Has a history of positive test result for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)

19. Has a concurrent illness not controlled by a stable therapeutic regimen

20. 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.

21. Has active substance or alcohol abuse (>21 drinks/week for males or >14 drinks/week for females)

22. 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

23. There is any reason the investigator deems exclusionary

24. Has donated blood within 8 weeks prior to Screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xeris Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrea Valasquez

Role: STUDY_DIRECTOR

Worldwide Clinical Trials

George Atiee

Role: PRINCIPAL_INVESTIGATOR

Worldwide Clinical Trials

Locations

World Wide Clinical Trials

San Antonio, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

DPI-201

Identifier Type: -

Identifier Source: org_study_id