Diabetes Mellitus, Type 1, Insulin-dependent Diabetes Mellitus
Conditions
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.
Interventions
DRUGPRAM9
SC injection
DRUGRegular Insulin + Pramlintide
Separate SC injections
DRUGRegular Insulin
SC injection
Sponsors
Xeris Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve 0-180 Minutes for Plasma Glucose >180 mg/dL | 0-180 minutes following administration of study drug | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Proportional Time After Glucose Challenge for Plasma Glucose Levels Between 126 to 180 mg/dL | During 40 to 180 minutes post-injection of study drug | 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. |
| Area Under the Concentration (AUC) Curve for Plasma Glucose | Up to 360 minutes following administration of study drug | 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 |
| Area Over the Concentration (AOC) Curve for Plasma Glucose | Up to 360 minutes following administration of study drug | 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 |
| Plasma Glucose Cmax | Up to 360 minutes following administration of study drug | The maximum measured glucose concentrations over the time span. |
| Plasma Glucose Tmax | Up to 360 minutes following administration of study drug | The time to maximum measured glucose concentrations. |
| Mean Proportional Time for Plasma Glucose Levels | Up to 360 minutes following administration of study drug | 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 |
| Pramlintide Tmax | Up to 360 minutes following administration of study drug | The time to maximum measured pramlintide concentrations. |
| Pramlintide Area Under the Concentration (AUC) Curve | Up to 360 minutes following administration of study drug | The pramlintide area under the concentration time curve after study drug administration (arithmetic mean). |
| Insulin Cmax | Up to 360 minutes following administration of study drug | The maximum measured insulin concentrations (arithmetic mean) |
| Insulin Tmax | Up to 360 minutes following administration of study drug | The time to maximum measured insulin concentrations. |
| Insulin Area Under the Concentration (AUC) Curve | Up to 360 minutes following administration of study drug | The insulin area under the concentration time curve after study drug administration. |
| Pramlintide Cmax | Up to 360 minutes following administration of study drug | The maximum measured pramlintide concentrations (arithmetic mean). |
Countries
United States
Participant flow
Recruitment details
The study was a 3-treatment, 6-sequence, 3-period crossover design where 18 eligible subjects randomized to 6 treatment sequences (3 subjects per sequence), with each subject scheduled to receive all 3 treatments.
Participants by arm
| Arm | Count |
|---|---|
| PRAM9 to Regular Insulin to Regular Insulin+Pramlintide PRAM9 (Xeris pramlintide + insulin co-formulation): SC injection Regular Insulin (Humulin®): SC injection Regular Insulin (Humulin®) + Pramlintide (Symlin®): Separate SC injections | 3 |
| Regular Insulin to Regular Insulin+Pramlintide to PRAM9 PRAM9 (Xeris pramlintide + insulin co-formulation): SC injection Regular Insulin (Humulin®): SC injection Regular Insulin (Humulin®) + Pramlintide (Symlin®): Separate SC injections | 3 |
| Regular Insulin+Pramlintide to PRAM9 to Regular Insulin PRAM9 (Xeris pramlintide + insulin co-formulation): SC injection Regular Insulin (Humulin®): SC injection Regular Insulin (Humulin®) + Pramlintide (Symlin®): Separate SC injections | 3 |
| PRAM9 to Regular Insulin+Pramlintide to Regular Insulin PRAM9 (Xeris pramlintide + insulin co-formulation): SC injection Regular Insulin (Humulin®): SC injection Regular Insulin (Humulin®) + Pramlintide (Symlin®): Separate SC injections | 3 |
| Regular Insulin to PRAM9 to Regular Insulin+Pramlintide PRAM9 (Xeris pramlintide + insulin co-formulation): SC injection Regular Insulin (Humulin®): SC injection Regular Insulin (Humulin®) + Pramlintide (Symlin®): Separate SC injections | 3 |
| Regular Insulin+Pramlintide to Regular Insulin to PRAM9 PRAM9 (Xeris pramlintide + insulin co-formulation): SC injection Regular Insulin (Humulin®): SC injection Regular Insulin (Humulin®) + Pramlintide (Symlin®): Separate SC injections | 3 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Third Period | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Regular Insulin+Pramlintide to Regular Insulin to PRAM9 | Total | PRAM9 to Regular Insulin to Regular Insulin+Pramlintide | Regular Insulin to Regular Insulin+Pramlintide to PRAM9 | Regular Insulin+Pramlintide to PRAM9 to Regular Insulin | PRAM9 to Regular Insulin+Pramlintide to Regular Insulin | Regular Insulin to PRAM9 to Regular Insulin+Pramlintide |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 18 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants |
| Age, Continuous | 49.3 years STANDARD_DEVIATION 4.73 | 43.9 years STANDARD_DEVIATION 12.27 | 46.7 years STANDARD_DEVIATION 21.36 | 45.0 years STANDARD_DEVIATION 18.68 | 42.3 years STANDARD_DEVIATION 14.5 | 38.0 years STANDARD_DEVIATION 5.57 | 42.0 years STANDARD_DEVIATION 9.54 |
| Body Mass Index | 26.183 kg/m^2 STANDARD_DEVIATION 1.669 | 26.044 kg/m^2 STANDARD_DEVIATION 2.562 | 26.543 kg/m^2 STANDARD_DEVIATION 3.06 | 24.340 kg/m^2 STANDARD_DEVIATION 3.196 | 28.267 kg/m^2 STANDARD_DEVIATION 3.248 | 24.313 kg/m^2 STANDARD_DEVIATION 2.039 | 26.620 kg/m^2 STANDARD_DEVIATION 1.257 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 6 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 12 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 175.00 cm STANDARD_DEVIATION 9.034 | 170.57 cm STANDARD_DEVIATION 11.642 | 175.43 cm STANDARD_DEVIATION 7.643 | 173.20 cm STANDARD_DEVIATION 15.552 | 170.47 cm STANDARD_DEVIATION 14.332 | 160.17 cm STANDARD_DEVIATION 5.299 | 169.17 cm STANDARD_DEVIATION 17.208 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 17 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 3 participants | 18 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants |
| Sex: Female, Male Female | 1 Participants | 10 Participants | 0 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants |
| Weight | 80.53 kg STANDARD_DEVIATION 11.869 | 75.99 kg STANDARD_DEVIATION 12.407 | 81.30 kg STANDARD_DEVIATION 4.952 | 72.23 kg STANDARD_DEVIATION 2.902 | 83.43 kg STANDARD_DEVIATION 22.74 | 62.27 kg STANDARD_DEVIATION 4.099 | 76.20 kg STANDARD_DEVIATION 11.888 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 17 |
| other Total, other adverse events | 10 / 18 | 9 / 18 | 10 / 17 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 17 |
Outcome results
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
Time frame: 0-180 minutes following administration of study drug
Population: The number of participants analyzed were the number of participants with glucose \>180 mg/dL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRAM9 | Area Under the Curve 0-180 Minutes for Plasma Glucose >180 mg/dL | 5019.6 min*mg/dL | Standard Deviation 4276.53 |
| Regular Insulin + Pramlintide | Area Under the Curve 0-180 Minutes for Plasma Glucose >180 mg/dL | 4591.9 min*mg/dL | Standard Deviation 3095.53 |
| Regular Insulin | Area Under the Curve 0-180 Minutes for Plasma Glucose >180 mg/dL | 13317.5 min*mg/dL | Standard Deviation 5262.42 |
p-value: <0.0001ANOVA
p-value: 0.694ANOVA
p-value: <0.0001ANOVA
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
Time frame: Up to 360 minutes following administration of study drug
Population: The number of participants analyzed were the number of participants after study drug administration with evaluable glucose measurements.~(There was no data available for the analysis of AOC0-90 for plasma glucose \<54 mg/dL.)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRAM9 | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-360: <54 mg/dL | 658.3 min*mg/dL | Standard Deviation 753.4 |
| PRAM9 | Area Over the Concentration (AOC) Curve for Plasma Glucose | AUC 0-90: <54 mg/dL | 658.3 min*mg/dL | Standard Deviation 753.4 |
| PRAM9 | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-90: <70 mg/dL | 2565.0 min*mg/dL | Standard Deviation 1665.8 |
| PRAM9 | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-180: <54 mg/dL | 658.3 min*mg/dL | Standard Deviation 753.4 |
| PRAM9 | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-360: <70 mg/dL | 3243.0 min*mg/dL | Standard Deviation 2611.35 |
| PRAM9 | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-180: <70 mg/dL | 3243.0 min*mg/dL | Standard Deviation 2611.35 |
| Regular Insulin + Pramlintide | Area Over the Concentration (AOC) Curve for Plasma Glucose | AUC 0-90: <54 mg/dL | 677.5 min*mg/dL | Standard Deviation 890.36 |
| Regular Insulin + Pramlintide | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-180: <54 mg/dL | 677.5 min*mg/dL | Standard Deviation 890.36 |
| Regular Insulin + Pramlintide | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-360: <54 mg/dL | 3545.0 min*mg/dL | Standard Deviation 6603.37 |
| Regular Insulin + Pramlintide | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-90: <70 mg/dL | 2086.4 min*mg/dL | Standard Deviation 1355.66 |
| Regular Insulin + Pramlintide | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-180: <70 mg/dL | 2086.4 min*mg/dL | Standard Deviation 1355.66 |
| Regular Insulin + Pramlintide | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-360: <70 mg/dL | 3797.5 min*mg/dL | Standard Deviation 6070.52 |
| Regular Insulin | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-180: <54 mg/dL | 0 min*mg/dL | Standard Deviation 0 |
| Regular Insulin | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-360: <70 mg/dL | 8242.5 min*mg/dL | Standard Deviation 6016.84 |
| Regular Insulin | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-180: <70 mg/dL | 1874.0 min*mg/dL | Standard Deviation 2587.66 |
| Regular Insulin | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-360: <54 mg/dL | 7531.3 min*mg/dL | Standard Deviation 5681.44 |
| Regular Insulin | Area Over the Concentration (AOC) Curve for Plasma Glucose | AUC 0-90: <54 mg/dL | 0.0 min*mg/dL | Standard Deviation 0 |
| Regular Insulin | Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC 0-90: <70 mg/dL | 1010.0 min*mg/dL | Standard Deviation 337.27 |
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
Time frame: Up to 360 minutes following administration of study drug
Population: The number of participants analyzed were the number of participants after study drug administration with evaluable glucose measurements.~(The time period of 0 to 90 minutes after study drug administration with glucose \>250 mg/dL was not quantifiable.)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRAM9 | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-180: >180 mg/dL | 5019.6 min*mg/dL | Standard Deviation 4276.53 |
| PRAM9 | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-360: >180 mg/dL | 16255.8 min*mg/dL | Standard Deviation 13128.46 |
| PRAM9 | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-90: >180 mg/dL | 475.0 min*mg/dL | Standard Deviation 1163.51 |
| PRAM9 | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-360: >250 mg/dL | 6506.3 min*mg/dL | Standard Deviation 8153 |
| PRAM9 | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-180: >250 mg/dL | 1592.7 min*mg/dL | Standard Deviation 1813.87 |
| Regular Insulin + Pramlintide | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-180: >180 mg/dL | 4591.9 min*mg/dL | Standard Deviation 3095.53 |
| Regular Insulin + Pramlintide | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-90: >180 mg/dL | 0 min*mg/dL | Standard Deviation 0 |
| Regular Insulin + Pramlintide | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-360: >180 mg/dL | 16101.2 min*mg/dL | Standard Deviation 11859.68 |
| Regular Insulin + Pramlintide | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-180: >250 mg/dL | 1455.0 min*mg/dL | Standard Deviation 1783.26 |
| Regular Insulin + Pramlintide | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-360: >250 mg/dL | 6847.5 min*mg/dL | Standard Deviation 7282.23 |
| Regular Insulin | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-360: >250 mg/dL | 16572.5 min*mg/dL | Standard Deviation 26676 |
| Regular Insulin | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-180: >250 mg/dL | 6302.5 min*mg/dL | Standard Deviation 3495.22 |
| Regular Insulin | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-180: >180 mg/dL | 13317.5 min*mg/dL | Standard Deviation 5262.42 |
| Regular Insulin | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-360: >180 mg/dL | 22334.6 min*mg/dL | Standard Deviation 13794.26 |
| Regular Insulin | Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC 0-90: >180 mg/dL | 1108.3 min*mg/dL | Standard Deviation 1193.57 |
Secondary
Insulin Area Under the Concentration (AUC) Curve
The insulin area under the concentration time curve after study drug administration.
Time frame: Up to 360 minutes following administration of study drug
Population: The number of participants analyzed were the number of participants after study drug administration with evaluable insulin concentrations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRAM9 | Insulin Area Under the Concentration (AUC) Curve | AUC 0-180 | 90807.346 min*pg/mL | Standard Deviation 45238.6643 |
| PRAM9 | Insulin Area Under the Concentration (AUC) Curve | AUC 0-90 | 4332.201 min*pg/mL | Standard Deviation 27662.1733 |
| PRAM9 | Insulin Area Under the Concentration (AUC) Curve | AUC 0-360 | 150580.775 min*pg/mL | Standard Deviation 73403.0839 |
| Regular Insulin + Pramlintide | Insulin Area Under the Concentration (AUC) Curve | AUC 0-180 | 114109.946 min*pg/mL | Standard Deviation 49208.963 |
| Regular Insulin + Pramlintide | Insulin Area Under the Concentration (AUC) Curve | AUC 0-90 | 52936.566 min*pg/mL | Standard Deviation 25400.6054 |
| Regular Insulin + Pramlintide | Insulin Area Under the Concentration (AUC) Curve | AUC 0-360 | 182852.584 min*pg/mL | Standard Deviation 100930.8761 |
| Regular Insulin | Insulin Area Under the Concentration (AUC) Curve | AUC 0-90 | 59727.578 min*pg/mL | Standard Deviation 26405.0845 |
| Regular Insulin | Insulin Area Under the Concentration (AUC) Curve | AUC 0-360 | 269913.163 min*pg/mL | Standard Deviation 100898.6768 |
| Regular Insulin | Insulin Area Under the Concentration (AUC) Curve | AUC 0-180 | 143606.541 min*pg/mL | Standard Deviation 54329.1923 |
Comparison: AUC 0 to 90 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.p-value: <0.000190% CI: [43.59, 64.83]ANOVA
Comparison: AUC 0 to 90 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.p-value: 0.001890% CI: [54.02, 78.8]ANOVA
Comparison: AUC 0 to 90 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.p-value: 0.239190% CI: [101.33, 148.66]ANOVA
Comparison: AUC 0 to 180 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.p-value: <0.000190% CI: [47.58, 61.73]ANOVA
Comparison: AUC 0 to 180 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.p-value: 0.000290% CI: [62.99, 80.69]ANOVA
Comparison: AUC 0 to 180 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.p-value: 0.002690% CI: [116.01, 149.17]ANOVA
Comparison: AUC 0 to 360 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.p-value: <0.000190% CI: [46.74, 56.39]ANOVA
Comparison: AUC 0 to 360 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.p-value: 0.000390% CI: [71.39, 85.76]ANOVA
Comparison: AUC 0 to 360 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.p-value: <0.000190% CI: [138.91, 167.22]ANOVA
Secondary
Insulin Cmax
The maximum measured insulin concentrations (arithmetic mean)
Time frame: Up to 360 minutes following administration of study drug
Population: The number of participants analyzed were the number of participants after study drug administration with evaluable insulin measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRAM9 | Insulin Cmax | 724.97 pg/mL | Standard Deviation 345.106 |
| Regular Insulin + Pramlintide | Insulin Cmax | 912.09 pg/mL | Standard Deviation 393.686 |
| Regular Insulin | Insulin Cmax | 1198.70 pg/mL | Standard Deviation 439.528 |
Comparison: 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.p-value: <0.000190% CI: [44.51, 65.11]ANOVA
Comparison: 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.p-value: 0.019290% CI: [61.06, 87.67]ANOVA
Comparison: 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.p-value: 0.024490% CI: [113.1, 163.31]ANOVA
Secondary
Insulin Tmax
The time to maximum measured insulin concentrations.
Time frame: Up to 360 minutes following administration of study drug
Population: The number of participants analyzed were the number of participants after study drug administration with evaluable insulin concentrations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PRAM9 | Insulin Tmax | 120.0 minutes |
| Regular Insulin + Pramlintide | Insulin Tmax | 90.5 minutes |
| Regular Insulin | Insulin Tmax | 121.0 minutes |
Comparison: 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.p-value: 0.2541ANOVA
Comparison: 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.p-value: >0.9999ANOVA
Comparison: 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.p-value: 0.1747ANOVA
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.
Time frame: During 40 to 180 minutes post-injection of study drug
Population: The number of participants analyzed were the number of participants 0 to 90, 0 to 180, and 0 to 360 minutes after study drug administration with any evaluable plasma glucose concentration data. (While the number of participants noted for each data point had evaluable plasma glucose concentration data, not all of the participants had values in the range of plasma glucose concentration required for the analysis of the proportion of time with glucose concentrations in the specified range.)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRAM9 | Mean Proportional Time After Glucose Challenge for Plasma Glucose Levels Between 126 to 180 mg/dL | 11.0 percentage of time | Standard Deviation 11.41 |
| Regular Insulin + Pramlintide | Mean Proportional Time After Glucose Challenge for Plasma Glucose Levels Between 126 to 180 mg/dL | 10.7 percentage of time | Standard Deviation 19.38 |
| Regular Insulin | Mean Proportional Time After Glucose Challenge for Plasma Glucose Levels Between 126 to 180 mg/dL | 9.8 percentage of time | Standard Deviation 11.92 |
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
Time frame: Up to 360 minutes following administration of study drug
Population: The number of participants analyzed were the number of participants 0 to 90, 0 to 180, and 0 to 360 minutes after study drug administration with any evaluable plasma glucose concentration data. (While the number of participants noted for each datapoint had evaluable plasma glucose concentration data, not all of the participants had values in the range of plasma glucose concentration required for the analysis of the proportion of time with glucose concentrations in the specified range.)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRAM9 | Mean Proportional Time for Plasma Glucose Levels | <54 mg/dL: 0 to 90 minutes | 14.8 percentage of time | Standard Deviation 16.97 |
| PRAM9 | Mean Proportional Time for Plasma Glucose Levels | >180 mg/dL: 0 to 90 minutes | 5.6 percentage of time | Standard Deviation 13.61 |
| PRAM9 | Mean Proportional Time for Plasma Glucose Levels | <54 mg/dL: 0 to 180 minutes | 7.4 percentage of time | Standard Deviation 8.49 |
| PRAM9 | Mean Proportional Time for Plasma Glucose Levels | <70 mg/dL: 0 to 90 minutes | 46.7 percentage of time | Standard Deviation 26.53 |
| PRAM9 | Mean Proportional Time for Plasma Glucose Levels | <54 mg/dL: 0 to 360 minutes | 3.7 percentage of time | Standard Deviation 4.25 |
| PRAM9 | Mean Proportional Time for Plasma Glucose Levels | >180 mg/dL: 0 to 180 minutes | 33.3 percentage of time | Standard Deviation 19.61 |
| PRAM9 | Mean Proportional Time for Plasma Glucose Levels | <70 mg/dL: 0 to 180 minutes | 30.0 percentage of time | Standard Deviation 23.76 |
| PRAM9 | Mean Proportional Time for Plasma Glucose Levels | >180 mg/dL: 0 to 360 minutes | 45.8 percentage of time | Standard Deviation 24.79 |
| PRAM9 | Mean Proportional Time for Plasma Glucose Levels | >250 mg/dL: 0 to 180 minutes | 19.7 percentage of time | Standard Deviation 17.98 |
| PRAM9 | Mean Proportional Time for Plasma Glucose Levels | <70 mg/dL: 0 to 360 minutes | 15.0 percentage of time | Standard Deviation 11.88 |
| PRAM9 | Mean Proportional Time for Plasma Glucose Levels | >250 mg/dL: 0 to 360 minutes | 27.1 percentage of time | Standard Deviation 21.41 |
| Regular Insulin + Pramlintide | Mean Proportional Time for Plasma Glucose Levels | <70 mg/dL: 0 to 360 minutes | 28.1 percentage of time | Standard Deviation 39.88 |
| Regular Insulin + Pramlintide | Mean Proportional Time for Plasma Glucose Levels | <54 mg/dL: 0 to 90 minutes | 19.4 percentage of time | Standard Deviation 24.64 |
| Regular Insulin + Pramlintide | Mean Proportional Time for Plasma Glucose Levels | >180 mg/dL: 0 to 360 minutes | 45.1 percentage of time | Standard Deviation 23.21 |
| Regular Insulin + Pramlintide | Mean Proportional Time for Plasma Glucose Levels | <54 mg/dL: 0 to 180 minutes | 9.7 percentage of time | Standard Deviation 12.32 |
| Regular Insulin + Pramlintide | Mean Proportional Time for Plasma Glucose Levels | <54 mg/dL: 0 to 360 minutes | 43.1 percentage of time | Standard Deviation 49.72 |
| Regular Insulin + Pramlintide | Mean Proportional Time for Plasma Glucose Levels | >180 mg/dL: 0 to 90 minutes | 0.0 percentage of time | Standard Deviation 0 |
| Regular Insulin + Pramlintide | Mean Proportional Time for Plasma Glucose Levels | <70 mg/dL: 0 to 180 minutes | 20.6 percentage of time | Standard Deviation 12.72 |
| Regular Insulin + Pramlintide | Mean Proportional Time for Plasma Glucose Levels | <70 mg/dL: 0 to 90 minutes | 41.3 percentage of time | Standard Deviation 25.43 |
| Regular Insulin + Pramlintide | Mean Proportional Time for Plasma Glucose Levels | >250 mg/dL: 0 to 360 minutes | 28.6 percentage of time | Standard Deviation 19.81 |
| Regular Insulin + Pramlintide | Mean Proportional Time for Plasma Glucose Levels | >250 mg/dL: 0 to 180 minutes | 18.0 percentage of time | Standard Deviation 15.9 |
| Regular Insulin + Pramlintide | Mean Proportional Time for Plasma Glucose Levels | >180 mg/dL: 0 to 180 minutes | 31.3 percentage of time | Standard Deviation 13.44 |
| Regular Insulin | Mean Proportional Time for Plasma Glucose Levels | <70 mg/dL: 0 to 360 minutes | 52.3 percentage of time | Standard Deviation 42.33 |
| Regular Insulin | Mean Proportional Time for Plasma Glucose Levels | >180 mg/dL: 0 to 90 minutes | 17.6 percentage of time | Standard Deviation 16.72 |
| Regular Insulin | Mean Proportional Time for Plasma Glucose Levels | >180 mg/dL: 0 to 180 minutes | 58.7 percentage of time | Standard Deviation 14.57 |
| Regular Insulin | Mean Proportional Time for Plasma Glucose Levels | >180 mg/dL: 0 to 360 minutes | 50.8 percentage of time | Standard Deviation 18.25 |
| Regular Insulin | Mean Proportional Time for Plasma Glucose Levels | >250 mg/dL: 0 to 180 minutes | 40.3 percentage of time | Standard Deviation 15.01 |
| Regular Insulin | Mean Proportional Time for Plasma Glucose Levels | >250 mg/dL: 0 to 360 minutes | 33.3 percentage of time | Standard Deviation 16.67 |
| Regular Insulin | Mean Proportional Time for Plasma Glucose Levels | <54 mg/dL: 0 to 90 minutes | 0 percentage of time | Standard Deviation 0 |
| Regular Insulin | Mean Proportional Time for Plasma Glucose Levels | <54 mg/dL: 0 to 360 minutes | 52.1 percentage of time | Standard Deviation 40.15 |
| Regular Insulin | Mean Proportional Time for Plasma Glucose Levels | <70 mg/dL: 0 to 90 minutes | 19.4 percentage of time | Standard Deviation 5.56 |
| Regular Insulin | Mean Proportional Time for Plasma Glucose Levels | <70 mg/dL: 0 to 180 minutes | 22.2 percentage of time | Standard Deviation 34.47 |
| Regular Insulin | Mean Proportional Time for Plasma Glucose Levels | <54 mg/dL: 0 to 180 minutes | 0 percentage of time | Standard Deviation 0 |
Comparison: Plasma Glucose Levels: \>180 mg/dL: 0 to 90 minutesp-value: 0.04195% CI: [-41.23, -1.36]ANOVA
Comparison: Plasma Glucose Levels: \>180 mg/dL: 0 to 90 minutesp-value: 0.45395% CI: [-31.43, 16.54]ANOVA
Comparison: Plasma Glucose Levels: \>180 mg/dL: 0 to 90 minutesp-value: 0.16195% CI: [-8.46, 36.15]ANOVA
Comparison: Plasma Glucose \>180 mg/dL: 0 to 180 minutesp-value: <0.00195% CI: [-35.37, -12.48]ANOVA
Comparison: Plasma Glucose \>180 mg/dL: 0 to 180 minutesp-value: 0.56495% CI: [-7.8, 14]ANOVA
Comparison: Plasma Glucose \>180 mg/dL: 0 to 180 minutesp-value: <0.00195% CI: [15.96, 38.09]ANOVA
Comparison: Plasma Glucose \>180 mg/dL: 0 to 360 minutesp-value: 0.81395% CI: [-16.7, 13.22]ANOVA
Comparison: Plasma Glucose \>180 mg/dL: 0 to 360 minutesp-value: 0.7395% CI: [-11.47, 16.17]ANOVA
Comparison: Plasma Glucose \>180 mg/dL: 0 to 360 minutesp-value: 0.58295% CI: [-10.97, 19.15]ANOVA
Secondary
Plasma Glucose Cmax
The maximum measured glucose concentrations over the time span.
Time frame: Up to 360 minutes following administration of study drug
Population: The number of participants analyzed were the number of participants after study drug administration with evaluable glucose measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRAM9 | Plasma Glucose Cmax | 301.4 mg/dL | Standard Deviation 66.72 |
| Regular Insulin + Pramlintide | Plasma Glucose Cmax | 303.3 mg/dL | Standard Deviation 73.37 |
| Regular Insulin | Plasma Glucose Cmax | 339.9 mg/dL | Standard Deviation 162.73 |
Secondary
Plasma Glucose Tmax
The time to maximum measured glucose concentrations.
Time frame: Up to 360 minutes following administration of study drug
Population: The number of participants analyzed were the number of participants after study drug administration with evaluable glucose measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRAM9 | Plasma Glucose Tmax | 251.7 minutes | Standard Deviation 83.68 |
| Regular Insulin + Pramlintide | Plasma Glucose Tmax | 208.3 minutes | Standard Deviation 47.68 |
| Regular Insulin | Plasma Glucose Tmax | 150.0 minutes | Standard Deviation 49.75 |
Secondary
Pramlintide Area Under the Concentration (AUC) Curve
The pramlintide area under the concentration time curve after study drug administration (arithmetic mean).
Time frame: Up to 360 minutes following administration of study drug
Population: The number of participants analyzed were the number of participants after study drug administration with evaluable pramlintide concentrations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRAM9 | Pramlintide Area Under the Concentration (AUC) Curve | AUC 0-180 | 9021.278 min*pg/mL | Standard Deviation 4669.0851 |
| PRAM9 | Pramlintide Area Under the Concentration (AUC) Curve | AUC 0-360 | 9491.208 min*pg/mL | Standard Deviation 4974.949 |
| PRAM9 | Pramlintide Area Under the Concentration (AUC) Curve | AUC 0-90 | 5752.239 min*pg/mL | Standard Deviation 2964.034 |
| Regular Insulin + Pramlintide | Pramlintide Area Under the Concentration (AUC) Curve | AUC 0-180 | 11079.075 min*pg/mL | Standard Deviation 7836.2702 |
| Regular Insulin + Pramlintide | Pramlintide Area Under the Concentration (AUC) Curve | AUC 0-90 | 10317.775 min*pg/mL | Standard Deviation 6782.4249 |
| Regular Insulin + Pramlintide | Pramlintide Area Under the Concentration (AUC) Curve | AUC 0-360 | 11132.408 min*pg/mL | Standard Deviation 7948.9301 |
Comparison: AUC 0 to 90 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.p-value: 0.007590% CI: [45.41, 80.43]ANOVA
Comparison: AUC 0 to 180 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.p-value: 0.677390% CI: [70.14, 124.16]ANOVA
Comparison: AUC 0 to 360 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.p-value: 0.876890% CI: [72.94, 130.14]ANOVA
Secondary
Pramlintide Cmax
The maximum measured pramlintide concentrations (arithmetic mean).
Time frame: Up to 360 minutes following administration of study drug
Population: The number of participants analyzed were the number of participants after study drug administration with evaluable pramlintide measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRAM9 | Pramlintide Cmax | 99.22 pg/mL | Standard Deviation 41.403 |
| Regular Insulin + Pramlintide | Pramlintide Cmax | 278.37 pg/mL | Standard Deviation 148.512 |
Comparison: 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.p-value: <0.000190% CI: [31.36, 43.75]ANOVA
Secondary
Pramlintide Tmax
The time to maximum measured pramlintide concentrations.
Time frame: Up to 360 minutes following administration of study drug
Population: The number of participants analyzed were the number of participants after study drug administration with evaluable pramlintide concentrations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PRAM9 | Pramlintide Tmax | 40.5 minutes |
| Regular Insulin + Pramlintide | Pramlintide Tmax | 10.0 minutes |
Comparison: 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.p-value: <0.0001ANOVA