A Study of LY2608204 in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01247363
First received: November 22, 2010
Last updated: April 1, 2011
Last verified: April 2011
  Purpose

Safety study with multiple oral doses of LY2608204 given to patients with type 2 diabetes. Study subjects will receive once daily doses of LY2608204 for a total treatment duration of up to 28 days. In this study, each patient will receive increasing doses of LY2608204 until reaching the highest dose that they can tolerate.

Continuous glucose monitoring devices will be employed for each patient to monitor for hypoglycemia during study treatment. Dose titration and dose reduction is determined for each individual patient based on their safety and glycemic data.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: LY2608204
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Safety and Tolerability of Multiple Ascending Doses of LY2608204 in Patients With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Number of participants with clinically significant effects [ Time Frame: baseline to study completion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics, area under the curve (AUC) [ Time Frame: Days 1, 7, 14, 21, 28-30, 33 and 35 ] [ Designated as safety issue: No ]
  • Pharmacokinetics, Maximum concentration (Cmax) [ Time Frame: Days 1, 7, 14, 21, 28-30, 33 and 35 ] [ Designated as safety issue: No ]
  • Pharmacokinetics, time to maximum concentration (tmax) [ Time Frame: Days 1, 7, 14, 21, 28-30, 33 and 35 ] [ Designated as safety issue: No ]
  • Number of hypoglycemic events [ Time Frame: Day 1 through Day 29 ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: November 2010
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY2608204
Oral capsules of LY2608204 given once daily at a starting dose of 160mg, which may be titrated in 3 dose escalations to 240mg, 320mg and 400mg, with a 7-day treatment duration at each dose level for up to 28 days total treatment.
Drug: LY2608204
Administered orally.
Other Name: Glucokinase Activator

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients diagnosed with T2DM who are currently treated with diet/lifestyle measures alone or in combination with anti-diabetic agents, including insulins
  • Have fasting blood glucose (FBG) greater than or equal to 160 mg/dL, with a subset of patients with FBG greater than or equal to 190 mg/dL in at least 2 measurements on separate days
  • Have a glycated haemoglobin (HbA1c) level of greater than or equal to 8% and less than or equal to 11% at screening
  • If female, are not of child-bearing potential due to surgical sterilisation (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause
  • Are males or females who are at least 18 years old (for sites outside of Singapore) or at least 21 years old (for sites within Singapore) but no more than 70 years old (for all sites)
  • Body mass index (BMI) greater than 18.5 kg/m2 and less than 40.0 kg/m2
  • Have clinical laboratory test results within the normal range for the population or investigator site, or with abnormalities deemed clinically insignificant by the investigator
  • Have supine systolic blood pressure (SBP) greater than 160 mmHg and supine diastolic blood pressure (DBP) less than 100 mmHg
  • Have venous access sufficient to allow blood sampling as per the protocol
  • Are willing and able to comply with requirements for continuous glucose monitoring (CGM)
  • Are reliable and willing to make themselves available for the duration of the study and who will abide by the Clinical Research Unit (CRU) policy and procedure and study restrictions. This includes staying in-patient at the CRU for a total duration of up to 31 days
  • Have given written informed consent approved by Lilly and the ethical review board governing the site

Exclusion Criteria:

  • Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or use of a 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 scientifically or medically compatible with this study
  • Have significant history of past or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (other than diabetes), hematological, or neurological disorders capable of significantly altering the absorption, metabolism or elimination of drugs or of constituting a risk when taking the study drug formulations or interfering with the interpretation of data
  • Have a history of a seizure disorder
  • A corrected QT interval greater than 450 msec at screening or any personal history of ventricular tachycardia or unexplained syncope, or other abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participating in the study
  • Have family history of long QT syndrome or family history of sudden unexplained death
  • Use medications known to prolong the QT interval.
  • Have type 1 diabetes mellitus or a history of ketoacidosis or any other type of diabetes mellitus other than type 2
  • Use of any known inducers or inhibitors of CYP3A within 14 days prior to the first dosing with study drug or intended use during the study
  • History of a hypoglycemic event with acute mental status alteration that was not preceded by prodromal symptoms recognizable to the patient
  • Fasting serum triglycerides greater than 500mg/dl
  • Serum creatinine greater than 1.3 mg/dL in women, greater than 1.5 mg/dL in men
  • Clinical evidence of active diabetic proliferative retinopathy
  • Known clinically significant autonomic neuropathy as evidenced by urinary retention, orthostatic hypotension, diabetic diarrhea or gastroparesis
  • Clinically significant coronary events or symptoms within 6 months prior to study entry
  • Clinically significant peripheral vascular disease
  • Have known allergies to LY2608204 or related compounds
  • Evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies/antigen
  • Evidence of hepatitis B and/or positive hepatitis B surface antigen (HBsAg)
  • Donation or loss of blood equal to or exceeding 450 mL during the 3 months before the first administration of study drug
  • Patients who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) (1 unit equal to 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits) or patients unwilling to stop alcohol consumption 24 hours prior to admission until the completion of each in-patient study period
  • Patients who smoke more than 10 cigarettes or other tobacco products per day before study entry. Patients will not be allowed to smoke while in the study Unit
  • Have a history of drug or alcohol abuse
  • Intended use of over-the counter or prescription medications 7 and 14 days, respectively, prior to dosing. If this situation arises, inclusion of an otherwise suitable volunteer may be at the discretion of the investigator. Use of anti-diabetic medication [metformin, sulphonylureas, glinides, thiazolidinediones, acarbose, DPPIV inhibitors, Byetta (but not liraglutide)] by patients with type 2 diabetes mellitus is acceptable for this study
  • Have repeated alanine transaminase levels greater than 2.5 times the upper limit of the reference range at screening, as determined by the central laboratory
  • Have previously been enrolled in this clinical study or any other study of LY2608204.

Exclusion Criteria for EU/UK/US Site(s) only --

  • Evidence of hepatitis C and/or positive hepatitis C antibodies, at screening
  • Use of known drugs of abuse and/or positive findings on urinary drug screening, other than findings consistent with medication prescribed by the patient's physician or over-the-counter medications
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01247363

Locations
United States, Florida
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.
Miramar, Florida, United States, 33025
Singapore
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.
Singapore, Singapore, 117597
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT01247363     History of Changes
Other Study ID Numbers: 14130, I3P-FW-GKBE
Study First Received: November 22, 2010
Last Updated: April 1, 2011
Health Authority: United States: Food and Drug Administration
Singapore: Health Sciences Authority

Keywords provided by Eli Lilly and Company:
Diabetes glucokinase safety

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on July 22, 2014