Effects and Response of LY2605541 in Patients With Type 1 Diabetes Mellitus (BIDO)

Healthy Clinical Trial

— BIDO  

Official title:

Evaluation of the Effects of LY2605541 on Respiratory Quotient During Sleep and Response to Hyperinsulinemia Compared With That of Insulin Glargine in Patients With Type 1 Diabetes Mellitus (BIDO)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02211586
• Other study ID #: TRIMDFH 433903
• Secondary ID: B2901009
• Status: Completed
• Phase: Phase 1
• First received: July 28, 2014
• Last updated: January 12, 2017
• Start date: June 2014
• Est. completion date: March 2016

Study information

• Verified date: January 2017
• Source: Translational Research Institute for Metabolism and Diabetes, Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to see what effect this investigational drug has on the body, and whether it causes a change to how your body uses fats and sugars as fuel sources.

Description:

The primary objective is to assess the effect of daily subcutaneous injections of LY2605541 on sleep respiratory quotient, measured during the post-absorptive period (0000 to 0600 hours), compared to daily subcutaneous injections of insulin glargine, in patients with Type 1 diabetes mellitus.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: March 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Healthy subjects and patients with T1DM are eligible for enrollment in the study only if they meet all of the following criteria:

• Cohort A: are male or female patients with T1DM of duration >1 year, as determined by medical history and physical examination, and are receiving a basal insulin. The following insulins are permitted if the patient is prepared to transition to once daily injection of insulin glargine in the evening combined with prandial insulin use:

• Glargine (once or split dosing),

• Detemir (once or split dosing),

• Neutral Protamine Hagedorn (once or split dosing),

• regular (once or split dosing),

• Insulin pump with rapid acting insulins.

• Cohort B: are overtly healthy males or females, as determined by medical history and physical examination. male patients: agree to use a reliable method of birth control during the study and for 3 months following the last dose of the investigational product. Cohort B subjects are not required to use birth control as they will not receive any study drugs during this study. female patients: are women of child-bearing potential (women not surgically sterilized and between menarche and 2 years postmenopause) who test negative for pregnancy at the time of screening based on a urine pregnancy test and agree to use a reliable method of birth control (for example, use of oral contraceptives, Norplant®, or contraceptive transdermal patch; a reliable barrier method of birth control [diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam]; intrauterine device; sexual abstinence, or partner with vasectomy) during the study and until the time they complete the follow up visit. Cohort B subjects are not required to take contraceptive medication as they will not receive any study drugs during this study. or women not of child-bearing potential due to surgical sterilization (at least 6 weeks after surgical bilateral oophorectomy with or without hysterectomy or at least 6 weeks after tubal ligation) confirmed by medical history, or menopause.

Menopausal women include women with either:

1. spontaneous amenorrhea for at least 12 months, not induced by a medical condition such as anorexia nervosa and not taking medications during the amenorrhea that induced the amenorrhea (for example oral contraceptives, hormones, gonadotropin releasing hormone, anti-estrogens, selective estrogen receptor modulators, or chemotherapy) or

2. spontaneous amenorrhea for 6 to 12 months and a follicle-stimulating hormone level greater than 40 million international units/mL.

• are between the ages of 18 and 60 years of age, inclusive, at screening.

• have a body mass index of 19 to 30 kg/m2, inclusive.

• have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator.

• have venous access sufficient to allow for blood sampling and IV administration as per the protocol.

• are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.

• have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site.

• Cohort A (patients with T1DM) are required to have a glycated hemoglobin (HbA1c) of =9.5%.

Exclusion Criteria:

Cohort A - Patients with T1DM and Cohort B - Healthy Subjects Healthy subjects and patients with T1DM will be excluded from study enrollment if they meet any of the following criteria:

• are investigator site personnel directly affiliated with this study and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.

• are Lilly, Translational Research Institute, University of Wisconsin (UW) Office of Clinical Trials, UW Nutritional Sciences, UW Health West Endocrinology Clinic, or Covance employees

• are currently enrolled in a clinical trial involving an investigational product or off-label use of a drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.

• have participated, within the last 30 days, in a clinical trial involving an investigational product. If the previous investigational product has a long t1/2, 3 months or 5 half-lives (whichever is longer) should have passed.

• are persons who have previously completed or withdrawn from this study or any other study investigating LY2605541, and have previously received the investigational product.

• have an abnormal blood pressure that is clinically relevant to this study as determined by the investigator. Patients who are on antihypertensive medication are eligible for inclusion in the study, but the doses of the antihypertensive medication must have been stable for1 month and must not change during the study.

• have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine (except T1DM, Cohort A), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data.

• intend to start new concomitant medication during the study, including over-the-counter and herbal medication (vitamin/mineral supplements, and occasional acetaminophen are permitted). The use of topical medication may also be permitted if no evidence of a risk of systemic absorption exists with chronic dosing.

• intend to make dietary changes during the study, that may in the opinion of the investigator impact on body weight or the results of the study.

• have a previous history of heart disease including atrial fibrillation, QT prolongation, or angina.

• regularly use known drugs of abuse and/or show positive findings on urinary drug screening.

• show evidence of human immunodeficiency virus infection and/or positive human immunodeficiency virus antibodies.

• show evidence of hepatitis C and/or positive hepatitis C antibody.

• show evidence of hepatitis B and/or positive hepatitis B surface antigen.

• are women with a positive pregnancy test or women who are lactating.

• have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), or are unwilling to stop alcohol consumption for the duration of the study (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).

• have triglyceride levels >400 mg/dL (>4.5 mmol/L); if triglyceride is >400 mg/dL, one retest is allowed, per investigator discretion. Retest value must be <400mg/dL.

• suffer from insomnia, are shift workers, or have abnormal sleep patterns.

• are smokers.

• are excessive consumers of xanthines (more than 10 cups of tea, coffee, cola, or hot chocolate per day).

• in the opinion of the investigator or sponsor, are unsuitable for inclusion in the study.

Cohort A - Patients with T1DM

• have known allergies to LY2605541, related compounds or any components of the formulation, or history of significant atopy.

• have a previous history or family history of deep vein thrombosis.

• have a previous history of proliferative retinopathy.

• require treatment with any drug other than insulin to treat diabetes.

• have poorly controlled diabetes or are known to have poor awareness of hypoglycemia.

• have had more than 1 episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia) within the last 6 months.

• have had 2 or more emergency room visits or hospitalizations due to poor glucose control (hyperglycemias or diabetic ketoacidosis) within the last 6 months.

• have a level of insulin resistance, insulin sensitivity, or responsiveness to insulin (based on insulin doses) that, in the opinion of the investigator, would impact on the study results.

• use ß-blockers or medications that have been reported to impact on hypoglycemia awareness within 4 weeks before dosing, or during the study.

• require the use of diuretics within 4 weeks of dosing, or during the study.

• regularly use or intend to use any nutritional supplements, systemic corticosteroids, or any over-the-counter or prescription medications that affect blood glucose or the body's sensitivity to insulin or that promote weight loss within the 4 weeks before dosing, or during the study. Patients who agree to stop taking supplements prior to or at screening are permitted at the discretion of the investigator. Thyroxine replacement therapy, and hormone replacement therapy are permitted, however patients must have been on a stable dose for at least 6 weeks prior to dosing.

• are unwilling to transition to a single daily injection of insulin glargine in the evening prior to enrollment.

• have suffered significant blood loss or donated blood of more than 500 mL within the last month.

Cohort- B Healthy Subjects

-have used, or intend to use over-the-counter medication within 7 days or prescription medication within 14 days of the start of their respiratory quotient measurements (apart from contraceptive medication, vitamin/mineral supplements, and occasional acetaminophen).

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Healthy
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Insulin Glargine or LY2605541
When initiating LY2605541, the patient will administer their basal insulin dose of LY2605541 in addition to a tapered dose of insulin glargine. On Day -2, the patient will administer the determined dose of LY2605541 plus 50% of the determined dose of insulin glargine. On Day -1, the patient will administer the determined dose of LY2605541 plus 25% of the determined dose of insulin glargine. On Day 1, the patient will administer the determined dose of LY2605541 only (no insulin glargine). Stable doses of LY2605541 will be administered for a minimum period of 4 weeks.

Locations

Country	Name	City	State
United States	Translational Research Institute for Metabolism and Diabetes	Orlando	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Translational Research Institute for Metabolism and Diabetes, Florida	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

References & Publications (3)

Flint A, Raben A, Blundell JE, Astrup A. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord. 2000 Jan;24(1):38-48. — View Citation

Kim J, Heshka S, Gallagher D, Kotler DP, Mayer L, Albu J, Shen W, Freda PU, Heymsfield SB. Intermuscular adipose tissue-free skeletal muscle mass: estimation by dual-energy X-ray absorptiometry in adults. J Appl Physiol (1985). 2004 Aug;97(2):655-60. — View Citation

Porcellati F, Bolli GB, Fanelli CG. Pharmacokinetics and pharmacodynamics of basal insulins. Diabetes Technol Ther. 2011 Jun;13 Suppl 1:S15-24. doi: 10.1089/dia.2011.0038. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Respiratory Quotient	The primary parameter for statistical analysis will be sleep respiratory quotient.	23-hour

External Links

•   Florida Hospital Translational Research Institute for Metabolism and Diabetes. Please visit our webpage for more information.