← Trials/Trial dossier/NCT04074317
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
Lead sponsor
Asset
Pramlintide
Subcutaneous · Amylin analog
Listed sites
1
Recruiting sites
—
Enrollment
18
actual
Study population
Type 1 diabetes
Key I/E criteria
•BMI 18-35•HbA1c ≤10%
Primary endpoint
•Area Under the Curve 0-180 Minutes for Plasma Glucose >180 mg/dL
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
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.
Endpoints (13)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
Coverage by outcome category
Glycemic / diabetes
8 endpointsArea Under the Curve 0-180 Minutes for Plasma Glucose >180 mg/dL
Time frame:0-180 minutes following administration of study drug
concentration, improvement
Posted result
| Group | Value (mean), min*mg/dL | 95% CI |
|---|---|---|
| PRAM9 | 5019.6 | — |
| Regular Insulin + Pramlintide | 4591.9 | — |
| Regular Insulin | 13317.5 | — |
Mean Proportional Time for Plasma Glucose Levels
Time frame:Up to 360 minutes following administration of study drug
descriptive, improvement
Posted result
| Group | Value (mean), percentage of time | 95% CI |
|---|---|---|
| PRAM9>180 mg/dL: 0 to 90 minutes | 5.6 | — |
| >180 mg/dL: 0 to 180 minutes | 33.3 | — |
| >180 mg/dL: 0 to 360 minutes | 45.8 | — |
| >250 mg/dL: 0 to 180 minutes | 19.7 | — |
| >250 mg/dL: 0 to 360 minutes | 27.1 | — |
| <54 mg/dL: 0 to 90 minutes | 14.8 | — |
| <54 mg/dL: 0 to 180 minutes | 7.4 | — |
| <54 mg/dL: 0 to 360 minutes | 3.7 | — |
| <70 mg/dL: 0 to 90 minutes | 46.7 | — |
| <70 mg/dL: 0 to 180 minutes | 30.0 | — |
| <70 mg/dL: 0 to 360 minutes | 15.0 | — |
| Regular Insulin + Pramlintide>180 mg/dL: 0 to 90 minutes | 0.0 | — |
| >180 mg/dL: 0 to 180 minutes | 31.3 | — |
| >180 mg/dL: 0 to 360 minutes | 45.1 | — |
| >250 mg/dL: 0 to 180 minutes | 18.0 | — |
| >250 mg/dL: 0 to 360 minutes | 28.6 | — |
| <54 mg/dL: 0 to 90 minutes | 19.4 | — |
| <54 mg/dL: 0 to 180 minutes | 9.7 | — |
| <54 mg/dL: 0 to 360 minutes | 43.1 | — |
| <70 mg/dL: 0 to 90 minutes | 41.3 | — |
| <70 mg/dL: 0 to 180 minutes | 20.6 | — |
| <70 mg/dL: 0 to 360 minutes | 28.1 | — |
| Regular Insulin>180 mg/dL: 0 to 90 minutes | 17.6 | — |
| >180 mg/dL: 0 to 180 minutes | 58.7 | — |
| >180 mg/dL: 0 to 360 minutes | 50.8 | — |
| >250 mg/dL: 0 to 180 minutes | 40.3 | — |
| >250 mg/dL: 0 to 360 minutes | 33.3 | — |
| <54 mg/dL: 0 to 90 minutes | 0 | — |
| <54 mg/dL: 0 to 180 minutes | 0 | — |
| <54 mg/dL: 0 to 360 minutes | 52.1 | — |
| <70 mg/dL: 0 to 90 minutes | 19.4 | — |
| <70 mg/dL: 0 to 180 minutes | 22.2 | — |
| <70 mg/dL: 0 to 360 minutes | 52.3 | — |
Plasma Glucose Levels: \>180 mg/dL: 0 to 90 minutes
Plasma Glucose Levels: \>180 mg/dL: 0 to 90 minutes
Plasma Glucose Levels: \>180 mg/dL: 0 to 90 minutes
Plasma Glucose \>180 mg/dL: 0 to 180 minutes
Plasma Glucose \>180 mg/dL: 0 to 180 minutes
Plasma Glucose \>180 mg/dL: 0 to 180 minutes
Plasma Glucose \>180 mg/dL: 0 to 360 minutes
Plasma Glucose \>180 mg/dL: 0 to 360 minutes
Plasma Glucose \>180 mg/dL: 0 to 360 minutes
Mean Proportional Time After Glucose Challenge for Plasma Glucose Levels Between 126 to 180 mg/dL
Time frame:During 40 to 180 minutes post-injection of study drug
descriptive, improvement
Posted result
| Group | Value (mean), percentage of time | 95% CI |
|---|---|---|
| PRAM9 | 11.0 | — |
| Regular Insulin + Pramlintide | 10.7 | — |
| Regular Insulin | 9.8 | — |
Area Under the Concentration (AUC) Curve for Plasma Glucose
Time frame:Up to 360 minutes following administration of study drug
descriptive, improvement
Posted result
| Group | Value (mean), min*mg/dL | 95% CI |
|---|---|---|
| PRAM9AUC 0-90: >180 mg/dL | 475.0 | — |
| AUC 0-180: >180 mg/dL | 5019.6 | — |
| AUC 0-360: >180 mg/dL | 16255.8 | — |
| AUC 0-180: >250 mg/dL | 1592.7 | — |
| AUC 0-360: >250 mg/dL | 6506.3 | — |
| Regular Insulin + PramlintideAUC 0-90: >180 mg/dL | 0 | — |
| AUC 0-180: >180 mg/dL | 4591.9 | — |
| AUC 0-360: >180 mg/dL | 16101.2 | — |
| AUC 0-180: >250 mg/dL | 1455.0 | — |
| AUC 0-360: >250 mg/dL | 6847.5 | — |
| Regular InsulinAUC 0-90: >180 mg/dL | 1108.3 | — |
| AUC 0-180: >180 mg/dL | 13317.5 | — |
| AUC 0-360: >180 mg/dL | 22334.6 | — |
| AUC 0-180: >250 mg/dL | 6302.5 | — |
| AUC 0-360: >250 mg/dL | 16572.5 | — |
Area Over the Concentration (AOC) Curve for Plasma Glucose
Time frame:Up to 360 minutes following administration of study drug
descriptive, improvement
Posted result
| Group | Value (mean), min*mg/dL | 95% CI |
|---|---|---|
| PRAM9AUC 0-90: <54 mg/dL | 658.3 | — |
| AOC 0-180: <54 mg/dL | 658.3 | — |
| AOC 0-360: <54 mg/dL | 658.3 | — |
| AOC 0-90: <70 mg/dL | 2565.0 | — |
| AOC 0-180: <70 mg/dL | 3243.0 | — |
| AOC 0-360: <70 mg/dL | 3243.0 | — |
| Regular Insulin + PramlintideAUC 0-90: <54 mg/dL | 677.5 | — |
| AOC 0-180: <54 mg/dL | 677.5 | — |
| AOC 0-360: <54 mg/dL | 3545.0 | — |
| AOC 0-90: <70 mg/dL | 2086.4 | — |
| AOC 0-180: <70 mg/dL | 2086.4 | — |
| AOC 0-360: <70 mg/dL | 3797.5 | — |
| Regular InsulinAUC 0-90: <54 mg/dL | 0.0 | — |
| AOC 0-180: <54 mg/dL | 0 | — |
| AOC 0-360: <54 mg/dL | 7531.3 | — |
| AOC 0-90: <70 mg/dL | 1010.0 | — |
| AOC 0-180: <70 mg/dL | 1874.0 | — |
| AOC 0-360: <70 mg/dL | 8242.5 | — |
Plasma Glucose Cmax
Time frame:Up to 360 minutes following administration of study drug
concentration, descriptive
Posted result
| Group | Value (mean), mg/dL | 95% CI |
|---|---|---|
| PRAM9 | 301.4 | — |
| Regular Insulin + Pramlintide | 303.3 | — |
| Regular Insulin | 339.9 | — |
Plasma Glucose Tmax
Time frame:Up to 360 minutes following administration of study drug
descriptive
Posted result
| Group | Value (mean), minutes | 95% CI |
|---|---|---|
| PRAM9 | 251.7 | — |
| Regular Insulin + Pramlintide | 208.3 | — |
| Regular Insulin | 150.0 | — |
Insulin Area Under the Concentration (AUC) Curve
Time frame:Up to 360 minutes following administration of study drug
concentration, descriptive
Posted result
| Group | Value (mean), min*pg/mL | 95% CI |
|---|---|---|
| PRAM9AUC 0-90 | 4332.201 | — |
| AUC 0-180 | 90807.346 | — |
| AUC 0-360 | 150580.775 | — |
| Regular Insulin + PramlintideAUC 0-90 | 52936.566 | — |
| AUC 0-180 | 114109.946 | — |
| AUC 0-360 | 182852.584 | — |
| Regular InsulinAUC 0-90 | 59727.578 | — |
| AUC 0-180 | 143606.541 | — |
| AUC 0-360 | 269913.163 | — |
Safety / tolerability / PK
5 endpointsPramlintide Cmax
Time frame:Up to 360 minutes following administration of study drug
Cmax
concentration, descriptive
Posted result
| Group | Value (mean), pg/mL | 95% CI |
|---|---|---|
| PRAM9 | 99.22 | — |
| Regular Insulin + Pramlintide | 278.37 | — |
The statistical model was an analysis of variance (ANOVA) on the ln-transformed data with sequence, period, and treatment as fixed effect and subject nested within sequence as a random effect.
Pramlintide Tmax
Time frame:Up to 360 minutes following administration of study drug
Tmax
descriptive
Posted result
| Group | Value (median), minutes | 95% CI |
|---|---|---|
| PRAM9 | 40.5 | 21 – 150 |
| Regular Insulin + Pramlintide | 10.0 | 10 – 24 |
The statistical model was an analysis of variance (ANOVA) with sequence, period, and treatment as fixed effect and subject nested within sequence as a random effect.
Pramlintide Area Under the Concentration (AUC) Curve
Time frame:Up to 360 minutes following administration of study drug
AUC₀–∞
concentration, descriptive
Posted result
| Group | Value (mean), min*pg/mL | 95% CI |
|---|---|---|
| PRAM9AUC 0-90 | 5752.239 | — |
| AUC 0-180 | 9021.278 | — |
| AUC 0-360 | 9491.208 | — |
| Regular Insulin + PramlintideAUC 0-90 | 10317.775 | — |
| AUC 0-180 | 11079.075 | — |
| AUC 0-360 | 11132.408 | — |
Insulin Cmax
Time frame:Up to 360 minutes following administration of study drug
Cmax
concentration, descriptive
Posted result
| Group | Value (mean), pg/mL | 95% CI |
|---|---|---|
| PRAM9 | 724.97 | — |
| Regular Insulin + Pramlintide | 912.09 | — |
| Regular Insulin | 1198.70 | — |
The statistical model was ana analysis of variance (ANOVA) on the ln-transformed data with sequence, period, and treatment as fixed effect and subject nested within sequence as a random effect.
The statistical model was an analysis of variance (ANOVA) on the ln-transformed data with sequence, period, and treatment as fixed effect and subject nested within sequence as a random effect.
The statistical model was an analysis of variance (ANOVA) on the ln-transformed data with sequence, period, and treatment as fixed effect and subject nested within sequence as a random effect.
Insulin Tmax
Time frame:Up to 360 minutes following administration of study drug
Tmax
concentration, descriptive
Posted result
| Group | Value (median), minutes | 95% CI |
|---|---|---|
| PRAM9 | 120.0 | 0 – 241 |
| Regular Insulin + Pramlintide | 90.5 | 40 – 300 |
| Regular Insulin | 121.0 | 30 – 360 |
The statistical model was an analysis of variance (ANOVA) with sequence, period, and treatment as fixed effect and subject nested within sequence as a random effect.
The statistical model was an analysis of variance (ANOVA) with sequence, period, and treatment as fixed effect and subject nested within sequence as a random effect.
The statistical model was an analysis of variance (ANOVA) with sequence, period, and treatment as fixed effect and subject nested within sequence as a random effect.
Provenance
Sources
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.