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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PRAM9 to Regular Insulin to Regular Insulin+pramlintide | Experimental | Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin (Humulin®) to Regular Insulin+pramlintide (Symlin® pen) as separate SC injections |
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| Regular Insulin to Regular Insulin+pramlintide to PRAM9 | Experimental | Regular Insulin (Humulin®) to Regular Insulin+pamlintide (Symlin® pen) as separate SC injections to PRAM9 |
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| Regular Insulin+pramlintide to PRAM9 to Regular Insulin | Experimental | Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin |
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| PRAM9 to Regular Insulin+pramlintide to Regular Insulin | Experimental | Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin (Humulin®)+pramlintide (Symlin® pen) as separate SC injections to Regular Insulin |
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| Regular Insulin to PRAM9 to Regular Insulin+pramlintide |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PRAM9 | Drug | SC injection |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve 0-180 Minutes for Plasma Glucose >180 mg/dL | The PD effects on plasma glucose levels were compared among the treatment arms as defined by AUC0-180 (mg/dL * minutes) for plasma glucose >180 mg/dL | 0-180 minutes following administration of study drug |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Proportional Time for Plasma Glucose Levels | The mean proportional times were evaluated for the following Plasma Glucose Levels: >180 mg/dL, >250 mg/dL, <54 mg/dL, and <70 The mean proportional times evaluated for each Plasma Glucose Level were during the following post-study drug injection periods: 0 to 90 minutes, 0 to 180 minutes, 0 to 360 minutes | Up to 360 minutes following administration of study drug |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Andrea Valasquez | Worldwide Clinical Trials | Study Director |
| George Atiee | Worldwide Clinical Trials | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| World Wide Clinical Trials | San Antonio | Texas | 78217 | United States |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | Regular Insulin to Regular Insulin+Pramlintide to PRAM9 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Period |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 13, 2019 | Apr 26, 2021 |
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| Experimental |
Regular Insulin (Humulin®) to Xeris pramlintide + insulin co-formulation (PRAM9) to Regular Insulin+pramlintide (Symlin® pen) as separate SC injections to Regular Insulin |
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| Regular Insulin+pramlintide to Regular Insulin to PRAM9 | Experimental | 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) |
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| Regular Insulin + Pramlintide | Drug | Separate SC injections |
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| Regular Insulin | Drug | SC injection |
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| Mean Proportional Time After Glucose Challenge for Plasma Glucose Levels Between 126 to 180 mg/dL | The mean proportional times to plasma glucose levels between 126 to 180 mg/dL following a glucose challenge administered 30 minutes post study drug administration. | During 40 to 180 minutes post-injection of study drug |
| Area Under the Concentration (AUC) Curve for Plasma Glucose | AUC0-t (mg/dL*minutes) for plasma glucose X mg/dL, in which X = (>180 mg/dL, >250 mg/dL) and t = 90, 180, and 360 minutes | Up to 360 minutes following administration of study drug |
| Area Over the Concentration (AOC) Curve for Plasma Glucose | AOC0-t (mg/dL*minutes) for plasma glucose X mg/dL, in which X = <54 mg/dL and <70 mg/dL and t = 90, 180, and 360 minutes | Up to 360 minutes following administration of study drug |
| Plasma Glucose Cmax | The maximum measured glucose concentrations over the time span. | Up to 360 minutes following administration of study drug |
| Plasma Glucose Tmax | The time to maximum measured glucose concentrations. | Up to 360 minutes following administration of study drug |
| Pramlintide Cmax | The maximum measured pramlintide concentrations (arithmetic mean). | Up to 360 minutes following administration of study drug |
| Pramlintide Tmax | The time to maximum measured pramlintide concentrations. | Up to 360 minutes following administration of study drug |
| Pramlintide Area Under the Concentration (AUC) Curve | The pramlintide area under the concentration time curve after study drug administration (arithmetic mean). | Up to 360 minutes following administration of study drug |
| Insulin Cmax | The maximum measured insulin concentrations (arithmetic mean) | Up to 360 minutes following administration of study drug |
| Insulin Tmax | The time to maximum measured insulin concentrations. | Up to 360 minutes following administration of study drug |
| Insulin Area Under the Concentration (AUC) Curve | The insulin area under the concentration time curve after study drug administration. | Up to 360 minutes following administration of study drug |
PRAM9 (Xeris pramlintide + insulin co-formulation): SC injection Regular Insulin (Humulin®): SC injection Regular Insulin (Humulin®) + Pramlintide (Symlin®): Separate SC injections |
| FG002 | 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 |
| FG003 | 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 |
| FG004 | 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 |
| FG005 | 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 |
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| NOT COMPLETED |
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| Second Period |
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| Third Period |
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Baseline characteristics by enrollment arm.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | 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 |
| BG002 | 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 |
| BG003 | 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 |
| BG004 | 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 |
| BG005 | 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 |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Weight | Mean | Standard Deviation | kg |
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| Height | Mean | Standard Deviation | cm |
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| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | The number of participants analyzed were the number of participants with glucose >180 mg/dL. | Posted | Mean | Standard Deviation | min*mg/dL | 0-180 minutes following administration of study drug |
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| 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 | 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.) | Posted | Mean | Standard Deviation | percentage of time | Up to 360 minutes following administration of study drug |
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| 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. | 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.) | Posted | Mean | Standard Deviation | percentage of time | During 40 to 180 minutes post-injection of study drug |
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| 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 | 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.) | Posted | Mean | Standard Deviation | min*mg/dL | Up to 360 minutes following administration of study drug |
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| 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 | 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.) | Posted | Mean | Standard Deviation | min*mg/dL | Up to 360 minutes following administration of study drug |
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| Secondary | Plasma Glucose Cmax | The maximum measured glucose concentrations over the time span. | The number of participants analyzed were the number of participants after study drug administration with evaluable glucose measurements. | Posted | Mean | Standard Deviation | mg/dL | Up to 360 minutes following administration of study drug |
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| Secondary | Plasma Glucose Tmax | The time to maximum measured glucose concentrations. | The number of participants analyzed were the number of participants after study drug administration with evaluable glucose measurements. | Posted | Mean | Standard Deviation | minutes | Up to 360 minutes following administration of study drug |
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| Secondary | Pramlintide Cmax | The maximum measured pramlintide concentrations (arithmetic mean). | The number of participants analyzed were the number of participants after study drug administration with evaluable pramlintide measurements. | Posted | Mean | Standard Deviation | pg/mL | Up to 360 minutes following administration of study drug |
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| Secondary | Pramlintide Tmax | The time to maximum measured pramlintide concentrations. | The number of participants analyzed were the number of participants after study drug administration with evaluable pramlintide concentrations. | Posted | Median | Full Range | minutes | Up to 360 minutes following administration of study drug |
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| Secondary | Pramlintide Area Under the Concentration (AUC) Curve | The pramlintide area under the concentration time curve after study drug administration (arithmetic mean). | The number of participants analyzed were the number of participants after study drug administration with evaluable pramlintide concentrations. | Posted | Mean | Standard Deviation | min*pg/mL | Up to 360 minutes following administration of study drug |
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| Secondary | Insulin Cmax | The maximum measured insulin concentrations (arithmetic mean) | The number of participants analyzed were the number of participants after study drug administration with evaluable insulin measurements. | Posted | Mean | Standard Deviation | pg/mL | Up to 360 minutes following administration of study drug |
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| Secondary | Insulin Tmax | The time to maximum measured insulin concentrations. | The number of participants analyzed were the number of participants after study drug administration with evaluable insulin concentrations. | Posted | Median | Full Range | minutes | Up to 360 minutes following administration of study drug |
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| Secondary | Insulin Area Under the Concentration (AUC) Curve | The insulin area under the concentration time curve after study drug administration. | The number of participants analyzed were the number of participants after study drug administration with evaluable insulin concentrations. | Posted | Mean | Standard Deviation | min*pg/mL | Up to 360 minutes following administration of study drug |
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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).
A TEAE with onset on or after the first dose of study drug, any preexisting AE worsened in severity on or after first dose of study drug.
Assignment of a TEAE to a specific treatment group:
TEAEs missing relationship were assumed to be related to study drug for analysis purposes
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PRAM9 | PRAM9 (Xeris pramlintide + insulin co-formulation): SC injection | 0 | 18 | 0 | 18 | 10 | 18 |
| EG001 | Regular Insulin + Pramlintide | Regular Insulin (Humulin®) + Pramlintide (Symlin®): Separate SC injections | 0 | 18 | 0 | 18 | 9 | 18 |
| EG002 | Regular Insulin | Regular Insulin (Humulin®): SC injection | 0 | 17 | 0 | 17 | 10 | 17 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 22.0 | Non-systematic Assessment |
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| Asthenia | General disorders | MedDRA 22.0 | Non-systematic Assessment | includes administration site conditions |
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| Injection site bruising | General disorders | MedDRA 22.0 | Non-systematic Assessment | includes administration site conditions |
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| Injection site discomfort | General disorders | MedDRA 22.0 | Non-systematic Assessment | includes administration site conditions |
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| Thirst | General disorders | MedDRA 22.0 | Non-systematic Assessment | includes administration site conditions |
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| Vessel puncture site thrombosis | General disorders | MedDRA 22.0 | Non-systematic Assessment | includes administration site conditions |
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| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA 22.0 | Non-systematic Assessment |
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| Hypoglycemia | Metabolism and nutrition disorders | MedDRA 22.0 | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 22.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 22.0 | Non-systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA 22.0 | Non-systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 22.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dawn Harper, VP Clinical Devlopment | Xeris Pharmaceuticals Inc. | (215) 704-7290 | dharper@xerispharma.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 15, 2019 | Apr 26, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| C105254 | pramlintide |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| ANOVA |
| 0.694 |
| Equivalence |
Treatment groups were compared using an analysis of variance (ANOVA) model, including sequence, period, and treatment as fixed effects and patient within sequence as random effect. |
| ANOVA | <0.0001 | Equivalence | Treatment groups were compared using an analysis of variance (ANOVA) model, including sequence, period, and treatment as fixed effects and patient within sequence as random effect. |
Regular Insulin (Humulin®): SC injection
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