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

NCT02500979 | Completed Phase 1 Results

• 1 other identifier: D5570C00002
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 3

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.

Conditions

Type 1 Diabetes Mellitus

Keywords

Type 1 Diabetes Mellitus; Pramlintide

Outcome Measures

Primary Outcomes (1)

• Efficacy of Pramlintide by Measurement of 24-hour Tissue Mean Weighted Glucose (MWG) Obtained With Continuous Glucose Monitoring (CGM)

  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.

  24 h

Secondary Outcomes (14)

• Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Lunch

  3 hours

• Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Dinner

  2 hours

• Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Breakfast

  2 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)

  24 h

• Efficacy of Pramlintide by Measurement of Absolute 24-hour Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC)

  24 h

Study Arms (2)

Pramlintide acetate & regular insulin

EXPERIMENTAL

Pramlintide will be adiministered by sc infusion at a concentration of 1000ug/mL

Drug: Pramlintide acetate; Drug: Lispro insulin U-100; Drug: Regular insulin U-100

Placebo and regular insulin

PLACEBO COMPARATOR

Placebo is similar sterile solution without pramlintide.

Drug: Placebo; Drug: Lispro insulin U-100; Drug: Regular insulin U-100

Interventions

Pramlintide acetate DRUG

Pramlintide acetate administered by a separate pump

Also known as: Pramlintide: SYMLIN

Pramlintide acetate & regular insulin

Placebo DRUG

Placebo administered by separate pump

Placebo and regular insulin

Lispro insulin U-100 DRUG

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)

Also known as: Humalog insulin lispro U-100

Placebo and regular insulin; Pramlintide acetate & regular insulin

Regular insulin U-100 DRUG

Use during two in-patient treatment periods (visits 4 and 5) and administered by separate pump

Also known as: Humulin R; U-100

Placebo and regular insulin; Pramlintide acetate & regular insulin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (3)

Research Site

Chula Vista, California, 91911, United States

Location

Research Site

Portland, Oregon, 97239, United States

Location

Research Site

Chattanooga, Tennessee, 37411, United States

Location

Related Publications (1)

• Riddle MC, Nahra R, Han J, Castle J, Hanavan K, Hompesch M, Huffman D, Strange P, Ohman 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.

  PMID: 30213882 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

pramlintide; Insulin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Due to the unavailability of the pramlintide assay, no data are presented for pramlintide PK parameters, and changes in pramlintide concentration could not be related to changes in insulin, plasma glucose, glucagon, or triglycerides.

Results Point of Contact

• Title: Dr. Peter Ohman
• Organization: AstraZeneca

Peter.Ohman@astrazeneca.com

+1 (301) 398-0120

Study Officials

• Peter Ohman, MD

  Medical Director AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2015
• First Posted: July 17, 2015
• Study Start: August 17, 2015
• Primary Completion: August 5, 2016
• Study Completion: August 5, 2016
• Last Updated: November 2, 2018
• Results First Posted: November 2, 2018

Record last verified: 2018-03

Locations

US (3)