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Trial record 31 of 2791 for:    Type 1 Diabetes

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
Last Update Posted : September 9, 2016
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Drug: Pramlintide acetate Drug: Placebo Drug: Lispro insulin U-100 Drug: Regular insulin U-100 Phase 1

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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : August 2015
Primary Completion Date : August 2016
Study Completion Date : August 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Pramlintide acetate & regular insulin
Pramlintide will be adiministered by sc infusion at a concentration of 1000ug/mL
Drug: Pramlintide acetate
Pramlintide acetate administered by a separate pump
Other Name: Pramlintide: SYMLIN
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
Placebo Comparator: Placebo and regular insulin
Placebo is similar sterile solution without pramlintide.
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


Outcome Measures

Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Pharmacokinetics analysis of pramlintide and insulin by measurement of Cmax of pramilintide and insulin [ Time Frame: 24 h ]
    Cmax of insulin and pramlintide.

  8. Pharmacokinetics analysis of pramlintide and insulin by measurement of tmax of pramilintide and insulin [ Time Frame: 24 h ]
    Tmax of insulin and pramlintide.

  9. 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.


Other Outcome Measures:
  1. 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.

  2. 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

  3. Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by assessment of hematology parameters [ Time Frame: 15 weeks ]
    Routine hematology laboratory assessments

  4. 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).

  5. 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

  6. 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 selfmonitored blood glucose (SMBG) and hypoglycemia diaries; composite measure

  7. Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by assessment of blood chemistry paramaters [ Time Frame: 15 weeks ]
    Routine blood chemistry laboratory assessments

  8. Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by assessment of urinalysis parameters [ Time Frame: 15 weeks ]
    Routine urinalysis laboratory assessments

  9. 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

  10. Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by drug screening [ Time Frame: 15 weeks ]
    Routine drug screening laboratory assessments

  11. Safety of subcutaneous pramlintide in subjects with Type 1 diabetes mellitus by pregnancy screening [ Time Frame: 15 weeks ]
    Routine pregnancy screening laboratory assessments


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02500979


Locations
United States, California
Research Site
Chula Vista, California, United States
United States, Oregon
Research Site
Portland, Oregon, United States
United States, Tennessee
Research Site
Chattanooga, Tennessee, United States
Sponsors and Collaborators
AstraZeneca
Juvenile Diabetes Research Foundation
Investigators
Study Director: Peter Ohman, MD Medical Director AstraZeneca
More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02500979     History of Changes
Other Study ID Numbers: D5570C00002
First Posted: July 17, 2015    Key Record Dates
Last Update Posted: September 9, 2016
Last Verified: September 2016

Keywords provided by AstraZeneca:
Type 1 Diabetes Mellitus; Pramlintide

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Pramlintide
Insulin
Insulin Lispro
Islet Amyloid Polypeptide
Hypoglycemic Agents
Physiological Effects of Drugs
Appetite Depressants
Anti-Obesity Agents
Amylin Receptor Agonists
Molecular Mechanisms of Pharmacological Action