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

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

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).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1; Insulin-dependent Diabetes Mellitus
• Intervention / Treatment: Drug: PRAM9; Drug: Regular Insulin + Pramlintide; Drug: Regular Insulin

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • World Wide Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: PRAM9; SC injection; Drug: Regular Insulin + Pramlintide; Separate SC injections; Drug: Regular Insulin; SC injection
Experimental: Regular Insulin to Regular Insulin+pramlintide to PRAM9; Regular Insulin (Humulin®) to Regular Insulin+pamlintide (Symlin® pen) as separate SC injections to PRAM9	Drug: PRAM9; SC injection; Drug: Regular Insulin + Pramlintide; Separate SC injections; Drug: Regular Insulin; SC injection
Experimental: 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	Drug: PRAM9; SC injection; Drug: Regular Insulin + Pramlintide; Separate SC injections; Drug: Regular Insulin; SC injection
Experimental: 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	Drug: PRAM9; SC injection; Drug: Regular Insulin + Pramlintide; Separate SC injections; Drug: Regular Insulin; SC injection
Experimental: 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	Drug: PRAM9; SC injection; Drug: Regular Insulin + Pramlintide; Separate SC injections; Drug: Regular Insulin; SC injection
Experimental: 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)	Drug: PRAM9; SC injection; Drug: Regular Insulin + Pramlintide; Separate SC injections; Drug: Regular Insulin; SC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve 0-180 Minutes for Plasma Glucose >180 mg/dL	The PD effects on plasma glucose levels were compared among the treatment arms as defined by AUC0-180 (mg/dL * minutes) for plasma glucose >180 mg/dL	0-180 minutes following administration of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Proportional Time for Plasma Glucose Levels	The mean proportional times were evaluated for the following Plasma Glucose Levels: >180 mg/dL, >250 mg/dL, <54 mg/dL, and <70 The mean proportional times evaluated for each Plasma Glucose Level were during the following post-study drug injection periods: 0 to 90 minutes, 0 to 180 minutes, 0 to 360 minutes	Up to 360 minutes following administration of study drug
Mean Proportional Time After Glucose Challenge for Plasma Glucose Levels Between 126 to 180 mg/dL	The mean proportional times to plasma glucose levels between 126 to 180 mg/dL following a glucose challenge administered 30 minutes post study drug administration.	During 40 to 180 minutes post-injection of study drug
Area Under the Concentration (AUC) Curve for Plasma Glucose	AUC0-t (mg/dL*minutes) for plasma glucose X mg/dL, in which X = (>180 mg/dL, >250 mg/dL) and t = 90, 180, and 360 minutes	Up to 360 minutes following administration of study drug
Area Over the Concentration (AOC) Curve for Plasma Glucose	AOC0-t (mg/dL*minutes) for plasma glucose X mg/dL, in which X = <54 mg/dL and <70 mg/dL and t = 90, 180, and 360 minutes	Up to 360 minutes following administration of study drug
Plasma Glucose Cmax	The maximum measured glucose concentrations over the time span.	Up to 360 minutes following administration of study drug
Plasma Glucose Tmax	The time to maximum measured glucose concentrations.	Up to 360 minutes following administration of study drug
Pramlintide Cmax	The maximum measured pramlintide concentrations (arithmetic mean).	Up to 360 minutes following administration of study drug
Pramlintide Tmax	The time to maximum measured pramlintide concentrations.	Up to 360 minutes following administration of study drug
Pramlintide Area Under the Concentration (AUC) Curve	The pramlintide area under the concentration time curve after study drug administration (arithmetic mean).	Up to 360 minutes following administration of study drug
Insulin Cmax	The maximum measured insulin concentrations (arithmetic mean)	Up to 360 minutes following administration of study drug
Insulin Tmax	The time to maximum measured insulin concentrations.	Up to 360 minutes following administration of study drug
Insulin Area Under the Concentration (AUC) Curve	The insulin area under the concentration time curve after study drug administration.	Up to 360 minutes following administration of study drug

Collaborators and Investigators

• Sponsor: Xeris Pharmaceuticals
• Investigators: Study Director: Andrea Valasquez, Worldwide Clinical Trials; Principal Investigator: George Atiee, Worldwide Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2019
• Primary Completion (Actual): April 2, 2020
• Study Completion (Actual): April 2, 2020

Study Registration Dates

• First Submitted: August 28, 2019
• First Submitted That Met QC Criteria: August 28, 2019
• First Posted (Actual): August 30, 2019

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Pramlintide
• Other Study ID Numbers: DPI-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No