Clinical trial NCT01372085: Single Dose Study in Healthy Participants to Investigate the Safety and Absorption of LY2584702
Official title: A Single Ascending Dose and Relative Bioavailability Study of LY2584702 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-06-13
Enrollment: 29
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-centre, placebo-controlled, two-part study in healthy participants.

Part A will be a single dose, single period, placebo-controlled pilot study to explore the safety, tolerability, absorption and pharmacodynamic \[effect of drug on a biological marker-phospho-S6 (pS6) levels in skin biopsies\] of a single dose of 25 milligrams (mg) LY2584702 Reference formulation (RF). Part B is a single dose, placebo-controlled, 4-period crossover study to primarily evaluate the absorption of the Test Formulation (TF) in comparison with the (RF) of LY2584702.


Eligibility criteria: Inclusion Criteria:

Male participants:

• Agree to use a reliable method of birth control during the study and for at least 1 month following the last dose of study drug

Female participants:

• Women not of childbearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Women with an intact uterus are deemed postmenopausal if they are greater than or equal to 45 years old, who have not taken hormones or oral contraceptives within the last year, and had cessation of menses for at least 1 year, or who have had 6 to 12 months of amenorrhea with follicle-stimulating hormone (FSH) levels consistent with postmenopausal state.

All participants:

* have a screening body mass index (BMI) of 18.5 to 32.0 kilograms per square meter (kg/m\^2), inclusive
* have clinical laboratory test results within the normal range for the population or investigator site, or with abnormalities deemed clinically insignificant by the investigator. In particular, participants should have normal or near normal screening liver tests at the discretion of the investigator
* have normal blood pressure and pulse rate (supine) at screening, or with minor deviations judged to be acceptable by the investigator
* have venous access sufficient to allow blood sampling 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

Exclusion Criteria

All participants:

* are currently enrolled in, have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product other than the investigational product 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. Participants that participate in Part A of this study may participate in Part B of the study if the first dosing in Part B is \>30 days after the dose of LY2584702 or placebo in Part A.
* have known allergies to LY2584702, or related compounds
* have an abnormality in the 12-lead electrocardiogram (ECG) \[including but not limited to Bazett's corrected QT (QTcB) interval \>450 milliseconds (msec) for men and \>470 msec for women\]
* have a history within the last 2 years or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, 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
* have a history of drug or alcohol abuse, or regularly use known drugs of abuse
* show evidence of human immunodeficiency virus infection and/or positive human immunodeficiency virus (HIV) antibodies
* show evidence of hepatitis B and/or positive hepatitis B surface antigen
* intend to use over-the-counter or prescription medication within 14 days prior to dosing or during the study
* use of herbal supplements, grapefruit juice, grapefruits, Seville orange juice, Seville oranges, or Starfruit within 7 days prior to study dosing or intended use during the study
* have donated blood of more than 450 milliliters (mL) within the last 3 months
* 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 from prior to dosing until the completion of each study period \[ unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits\]

Applicable for Part A only:

• have known allergies to lignocaine, adrenaline, tetracycline, or related compounds, which will be used in the skin biopsy procedure

Primary outcomes:
measure: Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Part A: Day 1 and Part B: Periods 1 to 4, Day 1 [Predose, 1 hour (h), 3 h, 4 h, 6 h, 10 h, 24 h, 48 h postdose]
Secondary outcomes:
measure: Pharmacokinetics, Area Under the Concentration-Time Curve (AUC)
timeFrame: Part A: Day 1 and Part B: Periods 1 to 4, Day 1 [Predose, 1 hour (h), 3 h, 4 h, 6 h, 10 h, 24 h, 48 h postdose]
measure: Part B: Baseline-Adjusted Change-From-Predose in the Concentration of Lipids (Total Cholesterol)
timeFrame: Part B: Baseline [Periods 1 and 4a (Day -1)], Periods 3, 4a (Day 1). Lipid concentration measurements were performed at time point 0 and 1 hour (h), 3 h, 4 h, 6 h, 10 h, and 24 h.
measure: Part A: QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
timeFrame: Part A: Baseline [Day 1 (Predose)] and Day 1 (3 h, 4 h, 6 h, and 24 h postdose)
measure: Part B: Average Time-Matched QT Interval Corrected by Fridericia's Formula (QTcF) Change From Baseline to Day 1
timeFrame: Part B: Baseline [Period 1 (Day -1)] and Periods 1 to 4 (Day 1). Electrocardiograms (ECG) were performed at time point 0 and 3 h, 4 h, 6 h, and 24 h.
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 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: