A Study of LY2624803 in Japanese Participants With Transient Insomnia

Phase 1

Completed

Conditions: Sleep Initiation and Maintenance Disorders

Interventions: Drug: LY2624803 - Solution
Drug: LY2624803 - Capsule
Drug: Placebo - Solution
Drug: Placebo - Capsule

Registration Number: NCT01784614

Lead Sponsor: Eli Lilly and Company

Brief Summary: The aim of this study is to learn how different doses of LY2624803 affect sleep in healthy Japanese participants. The study has four treatment periods. Participants will receive a single dose of LY2624803 or placebo in each treatment period.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

Inclusion Criteria

Overtly healthy males or female Japanese
Women of child-bearing potential, who test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of birth control during the study and for 3 months following the last dose of study drug
Body mass index (BMI) of 17.6 to 26.4 kilogram per meter square (kg/m^2), inclusive
Normal bedtime hours, with routine time spent in bed between 6.5 hours and 9 hours each night
Clinical laboratory test results within normal reference range
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 and able to follow study procedures
Have given written informed consent approved by Lilly and the ethical review board governing the site

Exclusion Criteria

Within 4 months of the initial dose of study drug, have received treatment with a drug that has not received regulatory approval for any indication
Persons who have previously completed or withdrawn from this study or any other study investigating LY2624803 after receiving study drug
Known allergies to LY2624803 or related compounds
Women who are lactating
Shift workers [those who shifted or plan to shift work within 7 days of any phase advance polysomnography (PSG) night] or any person who has crossed (or will have crossed) more than one time zone by aircraft within 3 days prior to entry
Have an irregular or altered sleep/wake schedule that is likely to prevent from keeping a regular sleep/wake schedule during the study
Regular napping (≥ 2 daytime naps/week by history)
Extreme morning type or evening type
Rhinitis, conjunctivitis, urticaria or chronic pain severe enough to interfere with sleep
Nocturia that would interfere with sleep assessment
Symptoms consistent with a sleep disorder or history of same
Evidence of significant active neuropsychiatric disease and in particular evidence of significant medical or psychiatric illness within the past 12 months that could contribute to insomnia
History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neurocardiogenic 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
History or presence of orthostatic signs and symptoms within 2 years
History of seizure or a close relative having a seizure disorder (such as epilepsy). History of a single febrile convulsion more than 10 years ago is acceptable. History of cranial trauma and loss of consciousness will be discussed prior to including any such participant
Abnormal movements observed outside of normal sleep time
Abnormal supine blood pressure and/or pulse rate
Participants with orthostatic hypotension at screening
An abnormality in the 12-lead electrocardiogram (ECG) that increases the risks associated with participating in the study
Regular use of known drugs of abuse and/or positive findings on urinary drug screening
Evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies
Evidence of hepatitis C and/or positive hepatitis C antibody
Evidence of hepatitis B and/or positive hepatitis B surface antigen
Evidence of syphilis infection and/or positive syphilis test
Use or intended use of prescription (except oral contraceptives), over-the-counter or herbal medication, specifically antihistamines, anticholinergic medications or any medications that affect sleepiness, within 28 days prior to Period 1 dosing and/or during the study
Participants who have donated more than 200 milliliters (mL) of blood or component blood within one month of screening, or those who have donated more than 400 mL of blood within 3 months of screening
History of smoking within the previous 6 months of screening
Participants who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), or participants unwilling to stop alcohol consumption for the period
Participants whose daily caffeine intake does not permit maintenance of usual sleep/wake schedule
No response to phase advance or a placebo responder
Sleep disorders detected during the PSG screening night
History or presence of breast cancer

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1.0 mg LY2624803	Placebo - Solution	Single dose of 1.0 mg LY2624803 administered orally in up to 2 of 4 treatment periods
Placebo	Placebo - Solution	Single dose of placebo administered orally in up to 1 of 4 treatment periods
3.0 mg LY2624803	Placebo - Solution	Single dose of 3.0 mg LY2624803 administered orally in up to 2 of 4 treatment periods
6.0 mg LY2624803	Placebo - Solution	Single dose of 6.0 mg LY2624803 administered orally in up to 2 of 4 treatment periods
0.1 milligrams (mg) LY2624803	LY2624803 - Solution	Single dose of 0.1 mg LY2624803 administered orally in up to 2 of 4 treatment periods
0.1 milligrams (mg) LY2624803	Placebo - Capsule	Single dose of 0.1 mg LY2624803 administered orally in up to 2 of 4 treatment periods
1.0 mg LY2624803	LY2624803 - Capsule	Single dose of 1.0 mg LY2624803 administered orally in up to 2 of 4 treatment periods
6.0 mg LY2624803	LY2624803 - Capsule	Single dose of 6.0 mg LY2624803 administered orally in up to 2 of 4 treatment periods
3.0 mg LY2624803	LY2624803 - Capsule	Single dose of 3.0 mg LY2624803 administered orally in up to 2 of 4 treatment periods
Placebo	Placebo - Capsule	Single dose of placebo administered orally in up to 1 of 4 treatment periods

Primary Outcome Measures

Name	Time	Method
Wake After Sleep Onset (WASO) With LY2624803 Compared to Placebo	8 hours in Periods 1, 2 and 3	WASO was calculated as total time in awake epochs between sleep onset time (first stage 2 epoch) and the end of the primary recording period (8 hours after lights -off). Data presented are Geometric Least Squares (LS) means. Geometric LS mean was calculated using mixed models analysis. The model included factors for treatment, treatment sequence, period and participants.

Secondary Outcome Measures

Name	Time	Method
Latency to Persistent Sleep (LPS)	8 hours in Periods 1, 2 and 3	LPS is defined as the latency from the lights-off time to the first stage 2 sleep followed by at least 10 consecutive minutes of sleep epochs. Data presented are Geometric LS means. Geometric LS mean was calculated using mixed models analysis. The model included factors for treatment, treatment sequence, period and participants.
Total Sleep Time (TST)	8 hours in Periods 1, 2 and 3	TST is defined as the total time in sleep epochs from sleep onset time to the end of the primary recording period (8 hours after lights -off). LS mean was calculated using mixed models analysis. The model included factors for treatment, treatment sequence, period and participants.
PK: Maximum Plasma Concentration (Cmax) of LY2624803 After Single Oral Dose in Period 4	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 10, 12, 18, and 42 hours post-dose in Period 4
PK: Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)] of LY2624803 After Single Oral Dose in Period 4	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 10, 12, 18, and 42 hours post-dose in Period 4

Trial Locations

Locations (1): 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.
🇯🇵
Sagamihara, Japan
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.
🇯🇵Sagamihara, Japan