Clinical trial NCT00883558: Safety Study of Subcutaneously-Injected Prandial INSULIN-PH20 NP Compared to Insulin Lispro Injection in Participants With Type 1 Diabetes Mellitus
Official title: A Phase II, Randomized, Open Label, 2-Way Crossover, Safety Study of Subcutaneously Injected Prandial INSULIN-PH20 NP Compared to Insulin Analog Injection in Patients With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Keywords: recombinant human hyaluronidase (rHuPH20)
Insulin lispro
regular human insulin
Lead sponsor: Halozyme Therapeutics
Sponsor class: INDUSTRY
First posted: 2009-04-17
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: Insulin lispro is approved by the Food and Drug Administration (FDA) for the treatment of diabetes mellitus. Recombinant human hyaluronidase (rHuPH20) is approved by the FDA as an aid to the absorption and dispersion of other injectable drugs. In this study, rHuPH20 combined with a non-preserved (NP) formulation of regular human insulin (INSULIN-PH20 NP) will be compared to insulin lispro with respect to absorption and action of insulin.

Detailed description: The purpose of this study is to compare the safety and tolerability of INSULIN-PH20 NP versus insulin lispro alone.

Eligibility criteria: Inclusion Criteria:

* Male or female of age 18 to 65 years, inclusive. Females of child-bearing potential must use a standard and effective means of birth control for the duration of the study.
* Participants with Type 1 diabetes mellitus (T1DM) (per World Health Organization \[WHO\] criteria) treated with insulin for ≥24 months.
* Participants who use an insulin infusion pump for basal insulin administration must be on the device for at least 90 days prior to screening.
* Body mass index (BMI) 18.0 to 35.0 kilograms per square meter (kg/m\^2), inclusive.
* Glycosylated hemoglobin A1c (HbA1c) ≤7.5 % based on central laboratory screening results.
* Fasting C-peptide \<0.6 nanograms per milliliter (ng/mL).
* Participants should be in good general health based on medical history and physical examination and without medical conditions that might prevent the completion of study drug injections and assessments required in this protocol.

Exclusion Criteria:

* Known or suspected allergy to any component of any of the study drugs in this study.
* Previous enrollment in this study. Participants who fail Screening may attempt to rescreen into the study.
* A participant who has proliferative retinopathy or maculopathy, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.
* As judged by the Investigator, clinically significant active disease of the gastrointestinal, cardiovascular (including a history of arrhythmia or conduction delays on electrocardiogram \[ECG\]), hepatic, neurological, renal, genitourinary, or hematological systems.
* As judged by the Investigator, uncontrolled hypertension (diastolic blood pressure ≥100 millimeters of mercury \[mmHg\] and/or systolic blood pressure ≥160 mmHg after 5 minutes in the supine position). Three attempts may be performed to measure blood pressure.
* History of any illness or disease that in the opinion of the Investigator might confound the results of the study or pose additional risk in administering the study drugs to the participant.
* As judged by the Investigator, clinically significant findings in routine laboratory data.
* Use of drugs (such as systemic corticosteroids) that may interfere with the interpretation of study results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia.
* Recurrent severe hypoglycemia (more than 2 episodes over the last 6 months) or hypoglycemic unawareness, as judged by the Investigator.
* Current addiction to alcohol or substances of abuse, as determined by the Investigator.
* Pregnancy, breast-feeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, intra-uterine device \[IUD\], oral or injectable contraceptives, or barrier methods).
* Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study.
* Receipt of any investigational drug within 4 weeks of Screening.
* Any condition (intrinsic or extrinsic) that in the judgment of the Investigator will interfere with study participation or evaluation of data. Examples would include: renal insufficiency (serum creatinine \>1.5 milligrams per deciliter \[mg/dL\] for males or \>1.4 mg/dL for females), congestive heart failure required medication treatment, and cardiac disease with New York Heart Association (NYHA) Functional Capacity of III/IV.

Primary outcomes:
measure: Postprandial Glucose Excursion
timeFrame: Week 14 and Week 26
Secondary outcomes:
measure: Time Spent With Blood Glucose Value Outside a 71-139 Milligrams Per Deciliter (mg/dL) Range During Continuous Glucose Monitoring
timeFrame: Week 14 and Week 26
measure: Number of Participants With Hypoglycemic Events
timeFrame: Baseline through Week 29
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Barbara Davis Center for Childhood Diabetes
state: Colorado
city: Miami
country: United States
facility: Diabetes Research Institute
state: Florida
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Butte
country: United States
facility: Mercury Street Medical
state: Montana
city: Durham
country: United States
facility: UNC Diabetes Care Center/Highgate Specialty Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Austin
country: United States
facility: Texas Diabetes and Endocrinology
state: Texas
city: Olympia
country: United States
facility: West Olympia Internal Medicine
state: Washington
Study officials:
affiliation: Halozyme Therapeutics
name: Douglas Muchmore, M.D.
role: STUDY_DIRECTOR
References: