Clinical trial NCT01358981: A Study of LY2881835 in Healthy People and People With Diabetes
Official title: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Escalating Oral Doses of LY2881835 in Healthy Subjects and 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: 2011-05-24
Enrollment: 18
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This will be the first study in which LY2881835 is given to humans in order to evaluate the safety and any side effects of LY2881835 in humans as well as how long LY2881835 stays in the body and its effect on blood sugar levels.

The study consists of two parts. In part A, healthy subjects will participate and in part B, patients with type 2 Diabetes Mellitus (T2DM) will participate.


Eligibility criteria: Inclusion Criteria:

All subjects:

* Are a healthy male or a healthy female who cannot become pregnant, or are patients with Type 2 Diabetes Mellitus (T2DM) who are not taking any drugs to lower blood sugar except metformin
* Have a body mass index (BMI) of at least 18.5 kilograms per meter squared (kg/m²) at screening
* Have blood pressure, pulse rate and clinical laboratory tests within the normal range for the population or investigator site, or with abnormalities deemed clinical insignificant by the investigator
* Have veins that are suitable for easy blood collection
* Are reliable and willing to be available for the whole study and are willing to follow study procedures
* Must have given written informed consent

Subjects with Type 2 Diabetes Mellitus (T2DM) only:

* Do not have any change to their diabetes treatment for at least 4 weeks prior to screening
* Have a glycosylated hemoglobin (HbA1c) level greater than or equal to 6% and less than or equal to 11% at screening

Exclusion Criteria:

All subjects:

* Are currently participating in or were in another new drug or medical research study in the last 30 days
* Have participated in this study before
* Have known allergies to compounds related to the study drug
* Currently have or used to have health problems or laboratory test results that in the opinion of the doctor, could interfere with understanding the results of this study
* Intend to use over-the-counter or prescription medications within 14 days prior to dosing or during the study. Hormone replacement therapy and intermittent use of paracetamol during the study is acceptable. For patients with Type 2 Diabetes Mellitus, medicines for control of high fats (For example, cholesterol), high blood pressure, are allowed.
* Have electrocardiogram (ECG) readings that are not suitable for the study
* Are unwilling to follow dietary restrictions/requirements for the study including 1) refrain from consuming foods or beverages containing grapefruit pomelo, star fruit, or Seville orange within 14 days of the start of the study drug dosing until collection of the last blood sample for drug assay and 2) consume only the meals provided during inpatient stays at the clinical research unit
* Have a history of drug or alcohol abuse
* Are infected with hepatitis B
* Are infected with human immunodeficiency disease virus (HIV)
* Have donated 450 milliliters (mL) or more of blood in the last 3 months or provided any blood donation within the last month from screening
* Have a regular alcohol intake greater than 21 units per week (males) and 14 units per week (females) or are not willing to abstain from alcohol while in the research unit
* Smoke more than 10 cigarettes per day or are not willing to abstain from smoking while at the clinic
* The study doctor thinks the subject should not participate for any other reasons

Subjects with Type 2 Diabetes Mellitus (T2DM) only:

* Have health complications due to poorly controlled diabetes as shown by blood and urine laboratory test results or based on physical examination and medical assessment, as determined by the study doctor
* Were hospitalised for poor control of their diabetes (ketoacidotic episode) in the last 6 months
* Currently using or have used insulin in the last 1 year to control their diabetes

Primary outcomes:
measure: Number of Participants With Clinically Significant Adverse Effects
timeFrame: Baseline to study completion up to 3 months
Secondary outcomes:
measure: Pharmacokinetics (PK): Area Under the Curve (AUC) of LY2881835
timeFrame: Part A: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24hours (h) post-dose; Part B: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) Of LY2881835
timeFrame: Part A: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose; Part B: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose
measure: Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of LY2881835
timeFrame: Part A: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose; Part B: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose
measure: Glucose Area Under the Effective Concentration Curve (AUEC)
timeFrame: Part A: Predose, 1.0, 1.5, 2.5, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18 and 24 h post-dose; Part B: Predose, 1.0, 1.5, 2.5, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18 and 24 h post-dose
measure: Glucagon-Like Peptide (Active GLP-1) Area Under the Effective Concentration Curve (AUEC)
timeFrame: Part A: Predose, 1.5 and 2.5 h post-dose; Part B: Predose, 1.5 and 2.5 h post-dose
measure: C-Peptide Area Under the Effective Concentration Curve (AUEC)
timeFrame: Part A: Predose, 1.0, 1.5, 2.5, 4, 5, 6 and 24 h post-dose; Part B: Predose, 1.0, 1.5, 2.5, 4, 5, 6 and 24 h post-dose
Other outcomes:
Locations:
city: Singapore
country: Singapore
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 9AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: