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CompletedNCT04074317Updated Mar 27, 2024Results posted

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

A Phase 2 interventional study of PRAM9 and Regular Insulin + Pramlintide in Diabetes Mellitus, Type 1 and Insulin-dependent Diabetes Mellitus, sponsored by Xeris Pharmaceuticals. Completed at 1 site in United States. Open to participants aged 18 Years to 64 Years. Per ClinicalTrials.gov, last updated 2024-03-27.

Sponsored by Xeris Pharmaceuticals · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
18
Allocation
Randomized
Ages
18 Years to 64 Years
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Diabetes Mellitus, Type 1
  • Insulin-dependent Diabetes Mellitus
03

Who can participate

Ages eligible
18 Years to 64 Years
Sexes eligible
All
Accepts 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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
18 participants (actual)

Study arms

  • 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 · Drug: Regular Insulin + Pramlintide · Drug: Regular Insulin

  • 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 · Drug: Regular Insulin + Pramlintide · Drug: Regular Insulin

  • 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 · Drug: Regular Insulin + Pramlintide · Drug: Regular Insulin

  • 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 · Drug: Regular Insulin + Pramlintide · Drug: Regular Insulin

  • 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 · Drug: Regular Insulin + Pramlintide · Drug: Regular Insulin

  • 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 · Drug: Regular Insulin + Pramlintide · Drug: Regular Insulin

Interventions

  • DrugPRAM9

    SC injection

  • DrugRegular Insulin + Pramlintide

    Separate SC injections

  • DrugRegular Insulin

    SC injection

05

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. Plasma Glucose Cmax

    The maximum measured glucose concentrations over the time span.

    Time frame: Up to 360 minutes following administration of study drug

  6. Plasma Glucose Tmax

    The time to maximum measured glucose concentrations.

    Time frame: Up to 360 minutes following administration of study drug

  7. Pramlintide Cmax

    The maximum measured pramlintide concentrations (arithmetic mean).

    Time frame: Up to 360 minutes following administration of study drug

  8. Pramlintide Tmax

    The time to maximum measured pramlintide concentrations.

    Time frame: Up to 360 minutes following administration of study drug

  9. 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

  10. Insulin Cmax

    The maximum measured insulin concentrations (arithmetic mean)

    Time frame: Up to 360 minutes following administration of study drug

  11. Insulin Tmax

    The time to maximum measured insulin concentrations.

    Time frame: Up to 360 minutes following administration of study drug

  12. 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

06

Results

Posted Mar 27, 2024

Participant flow

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.

First Period
Participant flow — First Period
MilestonePRAM9 to Regular Insulin to Regular Insulin+PramlintideRegular Insulin to Regular Insulin+Pramlintide to PRAM9Regular Insulin+Pramlintide to PRAM9 to Regular InsulinPRAM9 to Regular Insulin+Pramlintide to Regular InsulinRegular Insulin to PRAM9 to Regular Insulin+PramlintideRegular Insulin+Pramlintide to Regular Insulin to PRAM9
Started333333
Completed333333
Not completed000000
Second Period
Participant flow — Second Period
MilestonePRAM9 to Regular Insulin to Regular Insulin+PramlintideRegular Insulin to Regular Insulin+Pramlintide to PRAM9Regular Insulin+Pramlintide to PRAM9 to Regular InsulinPRAM9 to Regular Insulin+Pramlintide to Regular InsulinRegular Insulin to PRAM9 to Regular Insulin+PramlintideRegular Insulin+Pramlintide to Regular Insulin to PRAM9
Started333333
Completed333333
Not completed000000
Third Period
Participant flow — Third Period
MilestonePRAM9 to Regular Insulin to Regular Insulin+PramlintideRegular Insulin to Regular Insulin+Pramlintide to PRAM9Regular Insulin+Pramlintide to PRAM9 to Regular InsulinPRAM9 to Regular Insulin+Pramlintide to Regular InsulinRegular Insulin to PRAM9 to Regular Insulin+PramlintideRegular Insulin+Pramlintide to Regular Insulin to PRAM9
Started333333
Completed333233
Not completed000100
Withdrew: Withdrawal by subject000100

Outcome measures

PrimaryArea 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
Reported as:
Mean · min*mg/dL
Area Under the Curve 0-180 Minutes for Plasma Glucose >180 mg/dL
min*mg/dLPRAM9Regular Insulin + PramlintideRegular Insulin
Area Under the Curve 0-180 Minutes for Plasma Glucose >180 mg/dL5019.6 ± 4276.534591.9 ± 3095.5313317.5 ± 5262.42
Statistical analysis
  • PRAM9 vs Regular Insulin · ANOVA · p = <0.0001 (Least-squares geometric means for ln-transformed data.)
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = 0.694
  • Regular Insulin + Pramlintide vs Regular Insulin · ANOVA · p = <0.0001
SecondaryMean 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
Reported as:
Mean · percentage of time
Mean Proportional Time for Plasma Glucose Levels
percentage of timePRAM9Regular Insulin + PramlintideRegular Insulin
>180 mg/dL: 0 to 90 minutes5.6 ± 13.610.0 ± 0.0017.6 ± 16.72
>180 mg/dL: 0 to 180 minutes33.3 ± 19.6131.3 ± 13.4458.7 ± 14.57
>180 mg/dL: 0 to 360 minutes45.8 ± 24.7945.1 ± 23.2150.8 ± 18.25
>250 mg/dL: 0 to 180 minutes19.7 ± 17.9818.0 ± 15.9040.3 ± 15.01
>250 mg/dL: 0 to 360 minutes27.1 ± 21.4128.6 ± 19.8133.3 ± 16.67
<54 mg/dL: 0 to 90 minutes14.8 ± 16.9719.4 ± 24.640 ± 0
<54 mg/dL: 0 to 180 minutes7.4 ± 8.499.7 ± 12.320 ± 0
<54 mg/dL: 0 to 360 minutes3.7 ± 4.2543.1 ± 49.7252.1 ± 40.15
<70 mg/dL: 0 to 90 minutes46.7 ± 26.5341.3 ± 25.4319.4 ± 5.56
<70 mg/dL: 0 to 180 minutes30.0 ± 23.7620.6 ± 12.7222.2 ± 34.47
<70 mg/dL: 0 to 360 minutes15.0 ± 11.8828.1 ± 39.8852.3 ± 42.33
Statistical analysis
  • PRAM9 vs Regular Insulin · ANOVA · p = 0.041 · Ls mean difference: -21.29 · 95% CI -41.23 to -1.36
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = 0.453 · Ls mean difference: -7.45 · 95% CI -31.43 to 16.54
  • Regular Insulin + Pramlintide vs Regular Insulin · ANOVA · p = 0.161 · Ls mean difference: 13.85 · 95% CI -8.46 to 36.15
  • PRAM9 vs Regular Insulin · ANOVA · p = <0.001 · Ls mean difference: -23.93 · 95% CI -35.37 to -12.48
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = 0.564 · Ls mean difference: 3.10 · 95% CI -7.80 to 14.00
  • Regular Insulin + Pramlintide vs Regular Insulin · ANOVA · p = <0.001 · Ls mean difference: 27.03 · 95% CI 15.96 to 38.09
  • PRAM9 vs Regular Insulin · ANOVA · p = 0.813 · Ls mean difference: -1.74 · 95% CI -16.70 to 13.22
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = 0.730 · Ls mean difference: 2.35 · 95% CI -11.47 to 16.17
  • Regular Insulin + Pramlintide vs Regular Insulin · ANOVA · p = 0.582 · Ls mean difference: 4.09 · 95% CI -10.97 to 19.15
SecondaryMean 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
Reported as:
Mean · percentage of time
Mean Proportional Time After Glucose Challenge for Plasma Glucose Levels Between 126 to 180 mg/dL
percentage of timePRAM9Regular Insulin + PramlintideRegular Insulin
Mean Proportional Time After Glucose Challenge for Plasma Glucose Levels Between 126 to 180 mg/dL11.0 ± 11.4110.7 ± 19.389.8 ± 11.92
SecondaryArea 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
Reported as:
Mean · min*mg/dL
Area Under the Concentration (AUC) Curve for Plasma Glucose
min*mg/dLPRAM9Regular Insulin + PramlintideRegular Insulin
AUC 0-90: >180 mg/dL475.0 ± 1163.510 ± 01108.3 ± 1193.57
AUC 0-180: >180 mg/dL5019.6 ± 4276.534591.9 ± 3095.5313317.5 ± 5262.42
AUC 0-360: >180 mg/dL16255.8 ± 13128.4616101.2 ± 11859.6822334.6 ± 13794.26
AUC 0-180: >250 mg/dL1592.7 ± 1813.871455.0 ± 1783.266302.5 ± 3495.22
AUC 0-360: >250 mg/dL6506.3 ± 8153.006847.5 ± 7282.2316572.5 ± 26676.00
SecondaryArea 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
Reported as:
Mean · min*mg/dL
Area Over the Concentration (AOC) Curve for Plasma Glucose
min*mg/dLPRAM9Regular Insulin + PramlintideRegular Insulin
AUC 0-90: <54 mg/dL658.3 ± 753.40677.5 ± 890.360.0 ± 0.00
AOC 0-180: <54 mg/dL658.3 ± 753.40677.5 ± 890.360 ± 0
AOC 0-360: <54 mg/dL658.3 ± 753.403545.0 ± 6603.377531.3 ± 5681.44
AOC 0-90: <70 mg/dL2565.0 ± 1665.802086.4 ± 1355.661010.0 ± 337.27
AOC 0-180: <70 mg/dL3243.0 ± 2611.352086.4 ± 1355.661874.0 ± 2587.66
AOC 0-360: <70 mg/dL3243.0 ± 2611.353797.5 ± 6070.528242.5 ± 6016.84
SecondaryPlasma Glucose Cmax

The maximum measured glucose concentrations over the time span.

Time frame:
Up to 360 minutes following administration of study drug
Reported as:
Mean · mg/dL
Plasma Glucose Cmax
mg/dLPRAM9Regular Insulin + PramlintideRegular Insulin
Plasma Glucose Cmax301.4 ± 66.72303.3 ± 73.37339.9 ± 162.73
SecondaryPlasma Glucose Tmax

The time to maximum measured glucose concentrations.

Time frame:
Up to 360 minutes following administration of study drug
Reported as:
Mean · minutes
Plasma Glucose Tmax
minutesPRAM9Regular Insulin + PramlintideRegular Insulin
Plasma Glucose Tmax251.7 ± 83.68208.3 ± 47.68150.0 ± 49.75
SecondaryPramlintide Cmax

The maximum measured pramlintide concentrations (arithmetic mean).

Time frame:
Up to 360 minutes following administration of study drug
Reported as:
Mean · pg/mL
Pramlintide Cmax
pg/mLPRAM9Regular Insulin + PramlintideRegular Insulin
Pramlintide Cmax99.22 ± 41.403278.37 ± 148.512—
Statistical analysis
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = <0.0001 (Results of the statistical evaluation of ANOVA (alpha=0.05) for the hypothesis of equal treatment effects.) · Ratio of geometric least-squares means: 37.04 · 90% CI 31.36 to 43.75Ratio calculated as PRAM geometric least-squares mean divided by the Regular Insulin + Pramlintide geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
SecondaryPramlintide Tmax

The time to maximum measured pramlintide concentrations.

Time frame:
Up to 360 minutes following administration of study drug
Reported as:
Median · minutes
Pramlintide Tmax
minutesPRAM9Regular Insulin + PramlintideRegular Insulin
Pramlintide Tmax40.5 (21 to 150)10.0 (10 to 24)—
Statistical analysis
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = <0.0001 (Results of the statistical evaluation of ANOVA (alpha = 0.05) for the hypothesis of equal treatment effects.) · Ratio of least-square means: 435.96Ratio calculated as PRAM least-squares mean divided by the Regular Insulin + Pramlintide least-squares mean, expressed as a percentage.
SecondaryPramlintide 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
Reported as:
Mean · min*pg/mL
Pramlintide Area Under the Concentration (AUC) Curve
min*pg/mLPRAM9Regular Insulin + PramlintideRegular Insulin
AUC 0-905752.239 ± 2964.034010317.775 ± 6782.4249—
AUC 0-1809021.278 ± 4669.085111079.075 ± 7836.2702—
AUC 0-3609491.208 ± 4974.949011132.408 ± 7948.9301—
Statistical analysis
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = 0.0075 (Results of the statistical evaluation of ANOVA (alpha=0.05) for the hypothesis of equal treatment effects.) · Ratio of geometric least-squares means: 60.44 · 90% CI 45.41 to 80.43Ratio calculated as PRAM geometric least-squares mean divided by the Regular Insulin + Pramlintide geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = 0.6773 (Results of the statistical evaluation of ANOVA (alpha=0.05) for the hypothesis of equal treatment effects.) · Ratio of geometric least-squares means: 93.32 · 90% CI 70.14 to 124.16Ratio calculated as PRAM geometric least-squares mean divided by the Regular Insulin + Pramlintide geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = 0.8768 (Results of the statistical evaluation of ANOVA (alpha=0.05) for the hypothesis of equal treatment effects.) · Ratio of geometric least-squares means: 97.43 · 90% CI 72.94 to 130.14Ratio calculated as PRAM geometric least-squares mean divided by the Regular Insulin + Pramlintide geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
SecondaryInsulin Cmax

The maximum measured insulin concentrations (arithmetic mean)

Time frame:
Up to 360 minutes following administration of study drug
Reported as:
Mean · pg/mL
Insulin Cmax
pg/mLPRAM9Regular Insulin + PramlintideRegular Insulin
Insulin Cmax724.97 ± 345.106912.09 ± 393.6861198.70 ± 439.528
Statistical analysis
  • PRAM9 vs Regular Insulin · ANOVA · p = <0.0001 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05.) · Ratio of geometric least-squares means: 53.83 · 90% CI 44.51 to 65.11Ratio calculated as PRAM geometric least-squares mean divided by the Regular Insulin geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = 0.0192 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05.) · Ratio of geometric least-squares means: 73.16 · 90% CI 61.06 to 87.67Ratio calculated as PRAM geometric least-squares mean divided by the Regular Insulin + Pramlintide geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
  • Regular Insulin + Pramlintide vs Regular Insulin · ANOVA · p = 0.0244 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05.) · Ratio of geometric least-squares means: 135.91 · 90% CI 113.10 to 163.31Ratio calculated as Regular Insulin geometric least-squares mean divided by the Regular Insulin + Pramlintide geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
SecondaryInsulin Tmax

The time to maximum measured insulin concentrations.

Time frame:
Up to 360 minutes following administration of study drug
Reported as:
Median · minutes
Insulin Tmax
minutesPRAM9Regular Insulin + PramlintideRegular Insulin
Insulin Tmax120.0 (0 to 241)90.5 (40 to 300)121.0 (30 to 360)
Statistical analysis
  • PRAM9 vs Regular Insulin · ANOVA · p = 0.2541 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05) · Ratio of least-square means: 73.53Ratio calculated as PRAM least-squares mean divided by the Regular Insulin least-squares mean, expressed as a percentage.
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = >0.9999 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05.) · Ratio of least-squares means: 103.89Ratio calculated as PRAM least-squares mean divided by the Regular Insulin + Pramlintide least-squares mean, expressed as a percentage.
  • Regular Insulin + Pramlintide vs Regular Insulin · ANOVA · p = 0.1747 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05.) · Ratio of least-square means: 141.29Ratio calculated as Regular Insulin least-squares mean divided by the Regular Insulin + Pramlintide least-squares mean, expressed as a percentage.
SecondaryInsulin 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
Reported as:
Mean · min*pg/mL
Insulin Area Under the Concentration (AUC) Curve
min*pg/mLPRAM9Regular Insulin + PramlintideRegular Insulin
AUC 0-904332.201 ± 27662.173352936.566 ± 25400.605459727.578 ± 26405.0845
AUC 0-18090807.346 ± 45238.6643114109.946 ± 49208.9630143606.541 ± 54329.1923
AUC 0-360150580.775 ± 73403.0839182852.584 ± 100930.8761269913.163 ± 100898.6768
Statistical analysis
  • PRAM9 vs Regular Insulin · ANOVA · p = <0.0001 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05.) · Ratio of geometric least-squares means: 53.16 · 90% CI 43.59 to 64.83Ratio calculated as PRAM geometric least-squares mean divided by the Regular Insulin geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = 0.0018 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05) · Ratio of geometric least-squares means: 65.24 · 90% CI 54.02 to 78.80Ratio calculated as PRAM geometric least-squares mean divided by the Regular Insulin + Pramlintide geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
  • Regular Insulin + Pramlintide vs Regular Insulin · ANOVA · p = 0.2391 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05) · Ratio of geometric least-squares means: 122.73 · 90% CI 101.33 to 148.66Ratio calculated as Regular Insulin geometric least-squares mean divided by the Regular Insulin + Pramlintide geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
  • PRAM9 vs Regular Insulin · ANOVA · p = <0.0001 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05.) · Ratio of geometric least-squares means: 54.20 · 90% CI 47.58 to 61.73Ratio calculated as PRAM geometric least-squares mean divided by the Regular Insulin geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = 0.0002 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05) · Ratio of geometric least-squares means: 71.29 · 90% CI 62.99 to 80.69Ratio calculated as PRAM geometric least-squares mean divided by the Regular Insulin + Pramlintide geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
  • Regular Insulin + Pramlintide vs Regular Insulin · ANOVA · p = 0.0026 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05.) · Ratio of geometric least-squares means: 131.55 · 90% CI 116.01 to 149.17Ratio calculated as Regular Insulin geometric least-squares mean divided by the Regular Insulin + Pramlintide geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
  • PRAM9 vs Regular Insulin · ANOVA · p = <0.0001 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05.) · Ratio of geometric least-squares means: 51.34 · 90% CI 46.74 to 56.39Ratio calculated as PRAM geometric least-squares mean divided by the Regular Insulin geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
  • PRAM9 vs Regular Insulin + Pramlintide · ANOVA · p = 0.0003 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05.) · Ratio of geometric least-squares means: 78.24 · 90% CI 71.39 to 85.76Ratio calculated as PRAM geometric least-squares mean divided by the Regular Insulin + Pramlintide geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.
  • Regular Insulin + Pramlintide vs Regular Insulin · ANOVA · p = <0.0001 (Bonferroni-adjusted p-value to maintain the overall Type 1 error rate at 0.05.) · Ratio of geometric least-squares means: 152.41 · 90% CI 138.91 to 167.22Ratio calculated as Regular Insulin geometric least-squares mean divided by the Regular Insulin + Pramlintide geometric least-squares mean, expressed as a percentage. Confidence interval on the ratio, expressed as a percentage.

Adverse events

Collected over AEs were collected from time of ICF signature to up to the follow-up visit (7 to 11 days of last dose of study drug).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
PRAM90/18 (0%)0/18 (0%)10/18 (55.6%)
Regular Insulin + Pramlintide0/18 (0%)0/18 (0%)9/18 (50%)
Regular Insulin0/17 (0%)0/17 (0%)10/17 (58.8%)
Most frequent other events
Showing 10 of 13
Most frequent other events
EventPRAM9Regular Insulin + PramlintideRegular Insulin
HypoglycemiaMetabolism and nutrition disorders6/188/187/17
NauseaGastrointestinal disorders2/181/180/17
HeadacheNervous system disorders2/181/181/17
ThirstGeneral disorders0/180/181/17
Vessel puncture site thrombosisGeneral disorders0/180/181/17
Back painMusculoskeletal and connective tissue disorders0/180/181/17
DizzinessNervous system disorders0/181/181/17
AstheniaGeneral disorders1/180/180/17
Injection site bruisingGeneral disorders0/181/180/17
Injection site discomfortGeneral disorders1/181/180/17

Baseline characteristics

Baseline characteristics by enrollment arm.

Age, Categorical
Age, Categorical(Participants)PRAM9 to Regular Insulin to Regular Insulin+PramlintideRegular Insulin to Regular Insulin+Pramlintide to PRAM9Regular Insulin+Pramlintide to PRAM9 to Regular InsulinPRAM9 to Regular Insulin+Pramlintide to Regular InsulinRegular Insulin to PRAM9 to Regular Insulin+PramlintideRegular Insulin+Pramlintide to Regular Insulin to PRAM9Total
<=18 years0000000
Between 18 and 65 years33333318
>=65 years0000000
Age, Continuous
Age, Continuous(years)PRAM9 to Regular Insulin to Regular Insulin+PramlintideRegular Insulin to Regular Insulin+Pramlintide to PRAM9Regular Insulin+Pramlintide to PRAM9 to Regular InsulinPRAM9 to Regular Insulin+Pramlintide to Regular InsulinRegular Insulin to PRAM9 to Regular Insulin+PramlintideRegular Insulin+Pramlintide to Regular Insulin to PRAM9Total
Mean46.7 ± 21.3645.0 ± 18.6842.3 ± 14.5038.0 ± 5.5742.0 ± 9.5449.3 ± 4.7343.9 ± 12.27
Sex: Female, Male
Sex: Female, Male(Participants)PRAM9 to Regular Insulin to Regular Insulin+PramlintideRegular Insulin to Regular Insulin+Pramlintide to PRAM9Regular Insulin+Pramlintide to PRAM9 to Regular InsulinPRAM9 to Regular Insulin+Pramlintide to Regular InsulinRegular Insulin to PRAM9 to Regular Insulin+PramlintideRegular Insulin+Pramlintide to Regular Insulin to PRAM9Total
Female02232110
Male3110128
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PRAM9 to Regular Insulin to Regular Insulin+PramlintideRegular Insulin to Regular Insulin+Pramlintide to PRAM9Regular Insulin+Pramlintide to PRAM9 to Regular InsulinPRAM9 to Regular Insulin+Pramlintide to Regular InsulinRegular Insulin to PRAM9 to Regular Insulin+PramlintideRegular Insulin+Pramlintide to Regular Insulin to PRAM9Total
Hispanic or Latino0012216
Not Hispanic or Latino33211212
Unknown or Not Reported0000000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PRAM9 to Regular Insulin to Regular Insulin+PramlintideRegular Insulin to Regular Insulin+Pramlintide to PRAM9Regular Insulin+Pramlintide to PRAM9 to Regular InsulinPRAM9 to Regular Insulin+Pramlintide to Regular InsulinRegular Insulin to PRAM9 to Regular Insulin+PramlintideRegular Insulin+Pramlintide to Regular Insulin to PRAM9Total
American Indian or Alaska Native0000000
Asian0000000
Native Hawaiian or Other Pacific Islander0000000
Black or African American1000001
White23333317
More than one race0000000
Unknown or Not Reported0000000
Region of Enrollment
Region of Enrollment(participants)PRAM9 to Regular Insulin to Regular Insulin+PramlintideRegular Insulin to Regular Insulin+Pramlintide to PRAM9Regular Insulin+Pramlintide to PRAM9 to Regular InsulinPRAM9 to Regular Insulin+Pramlintide to Regular InsulinRegular Insulin to PRAM9 to Regular Insulin+PramlintideRegular Insulin+Pramlintide to Regular Insulin to PRAM9Total
United States33333318
Weight
Weight(kg)PRAM9 to Regular Insulin to Regular Insulin+PramlintideRegular Insulin to Regular Insulin+Pramlintide to PRAM9Regular Insulin+Pramlintide to PRAM9 to Regular InsulinPRAM9 to Regular Insulin+Pramlintide to Regular InsulinRegular Insulin to PRAM9 to Regular Insulin+PramlintideRegular Insulin+Pramlintide to Regular Insulin to PRAM9Total
Mean81.30 ± 4.95272.23 ± 2.90283.43 ± 22.7462.27 ± 4.09976.20 ± 11.88880.53 ± 11.86975.99 ± 12.407
Height
Height(cm)PRAM9 to Regular Insulin to Regular Insulin+PramlintideRegular Insulin to Regular Insulin+Pramlintide to PRAM9Regular Insulin+Pramlintide to PRAM9 to Regular InsulinPRAM9 to Regular Insulin+Pramlintide to Regular InsulinRegular Insulin to PRAM9 to Regular Insulin+PramlintideRegular Insulin+Pramlintide to Regular Insulin to PRAM9Total
Mean175.43 ± 7.643173.20 ± 15.552170.47 ± 14.332160.17 ± 5.299169.17 ± 17.208175.00 ± 9.034170.57 ± 11.642

1 further baseline measures are reported on the registry.

07

Study locations

1 site
  • World Wide Clinical Trials
    San Antonio, Texas 78217, United States
08

References and documents

Study documents

  • Study protocol · Dec 13, 2019
  • Statistical analysis plan · Nov 15, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT04074317
Lead sponsor
Xeris Pharmaceuticals
Responsible party
Sponsor
First posted
Aug 30, 2019
Start date
Aug 22, 2019
Primary completion
Apr 2, 2020
Completion
Apr 2, 2020
Results posted
Mar 27, 2024
Last update
Mar 27, 2024

Study contacts

Andrea Valasquez
study director · Worldwide Clinical Trials
George Atiee
principal investigator · Worldwide Clinical Trials

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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