Clinical trial NCT01253278: A Multiple-Ascending Dose Study in Type 2 Diabetes Mellitus Patients
Official title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of Multiple Escalating Oral Doses of LY2393910 in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-12-03
Enrollment: 38
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: The study drug LY2393910 is being evaluated as a possible treatment for diabetes. The primary purpose of a patient's participation in this study is to help answer the following research question(s), and not to provide treatment for diabetes:

* The safety of LY2393910 and any side effects that might be associated with it following 2 weeks of doses
* How long it takes the body to absorb and remove LY2393910 following dosing over 2 weeks
* How daily dosing of LY2393910 affects blood levels of sugar (glucose), insulin and other naturally occurring substances in your body
* How daily dosing of LY2393910 affects the cells that produce insulin
* Any differences in the above between LY2393910 taken as daily doses in the morning or in the evening


Eligibility criteria: Inclusion Criteria:

* Diagnosis of type 2 diabetes mellitus
* Must be on a stable treatment regimen (maintained on diet/exercise therapy with or without metformin) for at least 4 weeks prior to study entry
* Have a glycated haemoglobin (HbA1c) value greater than or equal to 6.5% and less than or equal to 10.0% on a stable treatment regimen
* Weigh 45.0 kg or more
* Have a Body Mass Index (BMI) greater than or equal to 18.5 and less than or equal to 40.0 kg/m2
* Are willing and able to conduct self-blood glucose monitoring tests

Exclusion Criteria:

* Are currently enrolled in, or discontinued within the last 30 days from a clinical trial involving use of an investigational drug or device other than the study drug used in this study, or are concurrently enrolled in any other type of medical research judged not to be compatible with this study
* Use of insulin for diabetic control for more than 6 consecutive days within 1 year prior to study entry
* Use of thiazolidinediones within 3 months, or other oral anti-diabetics (OADs), apart from metformin, within 1 month prior to study entry. Metformin is acceptable for this study
* Previous myocardial infarction, stroke or transient ischaemic event ('TIA'), or clinically significant coronary events or symptoms within 6 months prior to study entry
* Subjects who have any evidence of heart insufficiency, hypokalaemia, family history of long-QT-syndrome or are receiving other drugs which extend the QT interval
* Clinically significant peripheral vascular disease
* Clinical evidence of active diabetic proliferative retinopathy
* Known significant autonomic neuropathy
* Any patient having experienced a keto-acidotic episode requiring hospitalisation in the last 6 months
* Symptomatic hyperglycemia exhibited by significant osmotic symptoms (polyuria or polydipsia), unanticipated weight loss or dehydration
* Evidence of hepatitis B and/or positive hepatitis B surface antigen, at screening
* Subjects who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females)
* Subjects who are heavy smokers (\> 10 cigarettes, or equivalent, per day) or are unable or unwilling to refrain from nicotine during CRU admissions

Exclusion Criteria for EU Site only --

* Regular use of known drugs of abuse and/or positive findings on urinary drug screening
* Evidence of human immunodeficiency virus (HIV) and/or positive HIV antibodies
* Evidence of hepatitis C and/or positive hepatitis C antibodies

Primary outcomes:
measure: Number of Participants with Clinically Significant Effects
timeFrame: Over four weeks
Secondary outcomes:
measure: Pharmacokinetics of LY2393910, Area Under the Curve (AUC)
timeFrame: From predose Day 1 up until Day 19
measure: Change from baseline to day 28 in glucagon
timeFrame: Baseline, day 28
measure: Pharmacokinetics of LY2393910, maximum concentration (Cmax)
timeFrame: From predose Day 1 up until Day 19
measure: Change from baseline to day 28 in glucose-like peptide 1 (GLP-1)
timeFrame: Baseline, day 28
measure: Change from baseline to day 14 in insulin
timeFrame: baseline, day 14
measure: Change from baseline to day 14 in proinsulin
timeFrame: baseline, day 14
measure: Change from baseline to day 28 in glucose
timeFrame: baseline, day 28
measure: Change from baseline to day 14 in C-peptide
timeFrame: baseline, day 14
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: