Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect of a Fixed Pramlintide: Insulin Dose Ratio on Postprandial Glucose in Type 1 Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02500979
Recruitment Status : Completed
First Posted : July 17, 2015
Results First Posted : November 2, 2018
Last Update Posted : November 2, 2018
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE July 10, 2015
First Posted Date  ICMJE July 17, 2015
Results First Submitted Date  ICMJE August 2, 2017
Results First Posted Date  ICMJE November 2, 2018
Last Update Posted Date November 2, 2018
Actual Study Start Date  ICMJE August 17, 2015
Actual Primary Completion Date August 5, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 12, 2018)
Efficacy of Pramlintide by Measurement of 24-hour Tissue Mean Weighted Glucose (MWG) Obtained With Continuous Glucose Monitoring (CGM) [ Time Frame: 24 h ]
24-hour MWG mg/dL, defined as total area under the 24-hour tissue glucose curve obtained with CGM, divided by actual time span in the 24-hour period.
Original Primary Outcome Measures  ICMJE
 (submitted: July 15, 2015)
Efficacy of pramlintide by measurement of 24-hour mean weighted glucose (MWG) in mg/dL [ Time Frame: 24 h ]
24-hour MWG (mg/dL), defined as total area under the 24-hour blood glucose curve obtained with CGM, divided by 24 hours.
Change History Complete list of historical versions of study NCT02500979 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2018)
  • Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Lunch [ Time Frame: 3 hours ]
    Absolute postprandial plasma glucose AUC was measured for the first 3 hours (AUC0-3h) following lunch based on sample availability. (Sample times: 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
  • Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Dinner [ Time Frame: 2 hours ]
    Absolute postprandial plasma glucose AUC (AUC0-2h) was measured for the first 2 hours following dinner based on sample availability. (Sample times: 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours).
  • Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Breakfast [ Time Frame: 2 hours ]
    Absolute postprandial plasma glucose AUC (AUC0-2h) was measured for the first 2 hours following breakfast based on sample availability. (Sample times: 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours).
  • Efficacy of Pramlintide by Measurement of Incremental 24-hour Tissue Glucose Area Under the Plasma Concentration-time Curve (AUC) Obtained With Continuous Glucose Monitoring (CGM) [ Time Frame: 24 h ]
    Incremental (i.e., baseline-corrected) area under the 24-hour tissue glucose concentration curve (AUC0-24h) measured by continuous glucose monitoring (CGM) with a pre-test, non-fasting tissue glucose value as baseline. (Sample times: 0, 30 min, 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours, 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
  • Efficacy of Pramlintide by Measurement of Absolute 24-hour Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: 24 h ]
    Absolute mean area under the 24-hour plasma glucose concentration curve, measured as total area under the curve (0 to 24 hours). (Sample times: 0, 30 min, 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours, 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
  • Efficacy of Pramlintide by Measurement of Incremental 24-hour Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: 24 hours ]
    Incremental (i.e., baseline-corrected) mean area under the 24-hour plasma glucose concentration curve, measured as total area under the curve (0 to 24 hours). (Sample times: 0, 30 min, 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours, 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
  • Efficacy of Pramlintide Measured by Percent Time Spent in the Range of >70 mg/dL to <180 mg/dL Tissue Glucose Obtained With Continuous Glucose Monitoring (CGM) [ Time Frame: 24 h ]
    Percent time spent in the normoglycemic range of tissue glucose concentrations between >70 mg/dL and <180 mg/dL, measured by CGM. (Sample times: 0, 30 min, 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours, 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
  • Efficacy of Pramlintide by Measurement of Absolute 24-hour Plasma Glucagon Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: 24 h ]
    Absolute mean area under the 24-hour plasma glucagon concentration curve, measured as total area under the curve (total AUC0-24). (Sample times: 0, 30 min, 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours, 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
  • Efficacy of Pramlintide by Measurement of Incremental 24-hour Plasma Glucagon Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: 24 h ]
    Incremental (i.e., baseline-corrected) mean area under the 24-hour plasma glucagon concentration curve with a pre-test, non-fasting plasma glucagon value as baseline. (Sample times: 0, 30 min, 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours, 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
  • Fasting Plasma Glucose Concentration [ Time Frame: 12 hours after dinner meal ]
    Fasting plasma glucose concentration at 0600 hours (6:00 AM)
  • Pharmacokinetics of Insulin as Demonstrated by 24-hour Plasma Insulin Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: 24 hours ]
    Mean areas under the plasma insulin concentration curves for the 24-hour periods of pramlintide and placebo administration (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours [dinner], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours [breakfast], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours [lunch], 24 hours).
  • Pharmacokinetics of Insulin as Demonstrated by 24-hour Average Plasma Insulin Concentration. [ Time Frame: 24 hours ]
    Mean values of the average plasma insulin concentrations over the 24-hour periods of pramlintide and placebo administration. (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours [dinner], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours [breakfast], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours [lunch], 24 hours).
  • Pharmacokinetics of Insulin as Demonstrated by Maximum Plasma Insulin Concentration [ Time Frame: 24 hours ]
    Mean maximum plasma insulin concentrations over the 24-hour periods of pramlintide and placebo administration. (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours [dinner], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours [breakfast], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours [lunch], 24 hours).
  • Pharmacokinetics of Insulin as Demonstrated by the Time to the Maximum Plasma Insulin Concentration [ Time Frame: 24 hours ]
    Mean time to maximum plasma insulin concentrations over the 24-hour periods of pramlintide and placebo administration. (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours [dinner], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours [breakfast], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours [lunch], 24 hours).
Original Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2015)
  • Efficacy of pramlintide by measurement of total area under the 3-hour plasma glucose curves [ Time Frame: 24 h ]
    Total area under the 3-hour plasma glucose curves following each of 3 major meals based on the following components: total AUC0-3 breakfast, total AUC0-3 lunch, total AUC0-3 dinner, and average of the three total AUCs, during each treatment period.
  • Efficacy of pramlintide by measurement of percent time spent in the normoglycemic range of blood [ Time Frame: 24 h ]
    Percent time spent in the normoglycemic range of blood glucose concentrations between >70 mg/dL and <180 mg/dL, measured by CGM.
  • Efficacy of pramlintide by measurement of incremental area under the 24-hour blood glucose [ Time Frame: 24 h ]
    Incremental area under the 24-hour blood glucose concentration curve (incr AUC0-24), measured by Continuous glucose monitoring (CGM), with a pre-test, non-fasting blood glucose value as baseline.
  • Efficacy of pramlintide by measurement of mean area under the 24-hour plasma glucagon [ Time Frame: 24 h ]
    Mean area under the 24-hour plasma glucagon concentration curve, measured as both total area under the curve (total AUC0-24) and as incremental area under the curve (incr AUC0-24) with a pre-test, non-fasting venous glucagon value as baseline.
  • Efficacy of pramlintide by measurement of fasting plasma glucose concentration [ Time Frame: 24 h ]
    Fasting plasma glucose concentration at 0600 hours and at 0800 hours.
  • Pharmacokinetics analysis of pramlintide and insulin by measurement of AUC0-t of pramilintide and insulin [ Time Frame: 24 h ]
    AUC0-t of insulin and pramlintide.
  • Pharmacokinetics analysis of pramlintide and insulin by measurement of Cmax of pramilintide and insulin [ Time Frame: 24 h ]
    Cmax of insulin and pramlintide.
  • Pharmacokinetics analysis of pramlintide and insulin by measurement of tmax of pramilintide and insulin [ Time Frame: 24 h ]
    Tmax of insulin and pramlintide.
  • Pharmacokinetics analysis of pramlintide and insulin by measurement of average concentrations of pramilintide and insulin [ Time Frame: 24 h ]
    Average concentrations of insulin and pramlintide.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: July 15, 2015)
  • Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by assessment of Adverse events [ Time Frame: 15 weeks ]
    AEs, serious adverse events (SAEs), AEs leading to withdrawal, occurrences of biochemical or clinical hypoglycemia, clinical chemistry laboratory measurements, and symptoms that may also be related to intolerance, such as nausea or other gastrointestinal side effects.
  • Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by assessment of vital signs [ Time Frame: 15 weeks ]
    Vital signs (including blood pressure, heart rate, respiratory rate, and body temperature); composite measure
  • Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by assessment of hematology parameters [ Time Frame: 15 weeks ]
    Routine hematology laboratory assessments
  • Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by assessment of 12-lead Electrocardiograms [ Time Frame: 15 weeks ]
    12-lead electrocardiograms (ECGs).
  • Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by assessment of physical examinations [ Time Frame: 15 weeks ]
    Physical examinations, including assessment of: height, weight, and body mass index (weight [kg]/height2∙[m2]); composite measure
  • Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by evaluation of biochemical or clinical hypoglycemia [ Time Frame: 15 weeks ]
    Evaluate biochemical or clinical hypoglycemia on background insulin therapy alone throughout the study, outside the two inpatient treatment periods, using self-monitored blood glucose (SMBG) and hypoglycemia diaries; composite measure
  • Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by assessment of blood chemistry parameters [ Time Frame: 15 weeks ]
    Routine blood chemistry laboratory assessments
  • Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by assessment of urinalysis parameters [ Time Frame: 15 weeks ]
    Routine urinalysis laboratory assessments
  • Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by assessment of virus serology parameters [ Time Frame: 15 weeks ]
    Routine virus serology laboratory assessments
  • Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by drug screening [ Time Frame: 15 weeks ]
    Routine drug screening laboratory assessments
  • Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by pregnancy screening [ Time Frame: 15 weeks ]
    Routine pregnancy screening laboratory assessments
 
Descriptive Information
Brief Title  ICMJE Effect of a Fixed Pramlintide: Insulin Dose Ratio on Postprandial Glucose in Type 1 Diabetes Mellitus
Official Title  ICMJE A Randomized, Single-Blind, Two-Way Crossover, Placebo-Controlled Phase I Study to Compare the 24-hour Glucose Profile and Safety of Pramlintide and Insulin, Co-Administered in a Fixed-Dose Ratio, Versus Placebo and Insulin in Patients With Type 1 Diabetes Mellitus With Inadequate Glycemic Control
Brief Summary This study is designed to investigate the clinical efficacy and safety of pramlintide co-administered as a fixed-dose ratio with basal-bolus SC insulin, delivered simultaneously via 2 separate pumps, in subjects with type 1 diabetes who are failing to achieve the desired level of glycemic control using insulin therapy.
Detailed Description

Potentially eligible subjects with Type 1 diabetes mellitus who are treated with with a basal-bolus insulin regimen through multiple daily injections or insulin pump at a total daily insulin dose ≤60 U, will be eligible. Visit 1 is approximately 3-6 weeks prior to randomization. Given some variability in HbA1c and C-peptide assays, re-testing for HbA1c and C-peptide can be performed within 18 days from the initial visit. Visit 2 is approximately 2-5 weeks prior to randomization. Subjects are on lispro insulin throughout study except during Visit 4 and Visit 5, the domicile 24 hr treatment period, when they are switched to regular insulin U-100.

Screen failed patients may be re-screened for inclusion in the study, as long as re-screening takes place at least 3 months after the original screening visit. If a subject is re-screened, he/she must continue to meet all inclusion/exclusion criteria. All study procedures of initial Visit 1 must be repeated at the re-screening visit.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Type 1 Diabetes Mellitus
Intervention  ICMJE
  • Drug: Pramlintide acetate
    Pramlintide acetate administered by a separate pump
    Other Name: Pramlintide: SYMLIN
  • Drug: Placebo
    Placebo administered by separate pump
  • Drug: Lispro insulin U-100
    Subjects will be stabilized on a separate insulin pump and administered lispro insulin throughout the study, except during both inpatient treatment periods (Visit 4 and Visit 5)
    Other Name: Humalog insulin lispro U-100
  • Drug: Regular insulin U-100
    Use during two in-patient treatment periods (visits 4 and 5) and administered by separate pump
    Other Name: Humulin R; U-100
Study Arms  ICMJE
  • Experimental: Pramlintide acetate & regular insulin
    Pramlintide will be adiministered by sc infusion at a concentration of 1000ug/mL
    Interventions:
    • Drug: Pramlintide acetate
    • Drug: Lispro insulin U-100
    • Drug: Regular insulin U-100
  • Placebo Comparator: Placebo and regular insulin
    Placebo is similar sterile solution without pramlintide.
    Interventions:
    • Drug: Placebo
    • Drug: Lispro insulin U-100
    • Drug: Regular insulin U-100
Publications * Riddle MC, Nahra R, Han J, Castle J, Hanavan K, Hompesch M, Huffman D, Strange P, Öhman P. Control of Postprandial Hyperglycemia in Type 1 Diabetes by 24-Hour Fixed-Dose Coadministration of Pramlintide and Regular Human Insulin: A Randomized, Two-Way Crossover Study. Diabetes Care. 2018 Nov;41(11):2346-2352. doi: 10.2337/dc18-1091. Epub 2018 Sep 13.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 12, 2018)
34
Original Estimated Enrollment  ICMJE
 (submitted: July 15, 2015)
30
Actual Study Completion Date  ICMJE August 5, 2016
Actual Primary Completion Date August 5, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Provision of informed consent prior to any study-specific procedures
  • Female and/or male aged between 18 and 70 years
  • Must have a prior diagnosis of T1DM
  • Body mass index (BMI) <30 kg/m2
  • Subjects are not on current treatment with pramlintide (Symlin) and have not received pramlintide during the 6-month period prior to enrollment
  • Subjects should be willing to consume all of the components of the standardized meals administered during the study
  • Negative serum pregnancy test for female subjects of childbearing potential
  • Female subjects of childbearing potential must be 1 year postmenopausal, surgically sterile, or using an acceptable method of contraception for the duration of the study
  • Male subjects must be surgically sterile or using an acceptable method of contraception for the duration of the study

Exclusion Criteria:

  • Recurrent severe hypoglycemia requiring assistance within 6 months before screening
  • A history of hypoglycemia unawareness
  • A confirmed diagnosis of gastroparesis
  • Has been treated, is currently being treated, or is expected to require or undergo treatment with the following medications:
  • Any oral antihyperglycemic agent or any other injectable antihyperglycemic agent that is not insulin
  • Drugs that directly affect GI motility (eg, anticholinergic agents such as atropine)
  • Drugs that slow the intestinal absorption of nutrients (eg, α-glucosidase inhibitors
  • A history of gastric surgery (such as gastric banding, Roux- and Y bypass)
  • Is expected to require or undergo treatment with acetaminophen after enrollment and at any point during the study
  • Has experienced diabetic ketoacidosis within the last 24 weeks
  • History of hospitalization within the last 6 months for glycemic control (for both hyperglycemia or hypoglycemia)
  • Subject has any significant disease or disorder, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the results of the study, or the subject's ability to participate in the study
  • Any clinically relevant abnormal findings, which, in the opinion of the investigator, may put the subject at risk because of his/her participation in the study.
  • Pregnancy confirmed by a positive pregnancy test, or otherwise verified.
  • Breast feeding
  • Positive hepatitis C virus antibody (HCV Ab), hepatitis B virus surface antigen (HBsAg), hepatitis B virus core antibody (anti-Hbc), or human immunodeficiency virus 1/2 antibody (HIV-1/2 Ab) at Screening
  • History of, or current alcohol or drug abuse
  • Has donated blood within 2 months of Visit 1 (Screening) or is planning to donate blood during the study
  • Has had a major surgery or a blood transfusion within 2 months before Visit 1 (screening)
  • Participation in any clinical study with an investigational drug or new formulation of a marketed drug during the last 1 month prior to Visit 1
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02500979
Other Study ID Numbers  ICMJE D5570C00002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Juvenile Diabetes Research Foundation
Investigators  ICMJE
Study Director: Peter Ohman, MD Medical Director AstraZeneca
PRS Account AstraZeneca
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP