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

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04074317
• Other study ID #: DPI-201
• Status: Completed
• Phase: Phase 2
• Start date: August 22, 2019
• Est. completion date: April 2, 2020

Study information

• Verified date: February 2024
• Source: Xeris Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: April 2, 2020
• Est. primary completion date: April 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• PRAM9
SC injection
• Regular Insulin + Pramlintide
Separate SC injections
• Regular Insulin
SC injection

Locations

Country	Name	City	State
United States	World Wide Clinical Trials	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Xeris Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Plasma Glucose Cmax	The maximum measured glucose concentrations over the time span.	Up to 360 minutes following administration of study drug
Secondary	Plasma Glucose Tmax	The time to maximum measured glucose concentrations.	Up to 360 minutes following administration of study drug
Secondary	Pramlintide Cmax	The maximum measured pramlintide concentrations (arithmetic mean).	Up to 360 minutes following administration of study drug
Secondary	Pramlintide Tmax	The time to maximum measured pramlintide concentrations.	Up to 360 minutes following administration of study drug
Secondary	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
Secondary	Insulin Cmax	The maximum measured insulin concentrations (arithmetic mean)	Up to 360 minutes following administration of study drug
Secondary	Insulin Tmax	The time to maximum measured insulin concentrations.	Up to 360 minutes following administration of study drug
Secondary	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