A Study of LY2624803 in Japanese Participants With Transient Insomnia

• ClinicalTrials.gov Identifier: NCT01784614
• Recruitment Status: Completed
• First Posted: February 6, 2013
• Results First Posted: January 28, 2016
• Last Update Posted: January 28, 2016
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Sleep Initiation and Maintenance Disorders	Drug: LY2624803 - Solution; Drug: LY2624803 - Capsule; Drug: Placebo - Solution; Drug: Placebo - Capsule	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Official Title: Pharmacodynamics and Pharmacokinetics of Single Doses of LY2624803 in a 5-hour Phase Advance Model of Transient Insomnia in Healthy Japanese Subjects
• Study Start Date: September 2009
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: March 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: 0.1 milligrams (mg) LY2624803; Single dose of 0.1 mg LY2624803 administered orally in up to 2 of 4 treatment periods	Drug: LY2624803 - Solution; Administered orally as reconstituted solution; Drug: Placebo - Capsule; Administered orally as a capsule
Experimental: 1.0 mg LY2624803; Single dose of 1.0 mg LY2624803 administered orally in up to 2 of 4 treatment periods	Drug: LY2624803 - Capsule; Administered orally as a capsule; Drug: Placebo - Solution; Administered orally as solution
Experimental: 3.0 mg LY2624803; Single dose of 3.0 mg LY2624803 administered orally in up to 2 of 4 treatment periods	Drug: LY2624803 - Capsule; Administered orally as a capsule; Drug: Placebo - Solution; Administered orally as solution
Experimental: 6.0 mg LY2624803; Single dose of 6.0 mg LY2624803 administered orally in up to 2 of 4 treatment periods	Drug: LY2624803 - Capsule; Administered orally as a capsule; Drug: Placebo - Solution; Administered orally as solution
Placebo Comparator: Placebo; Single dose of placebo administered orally in up to 1 of 4 treatment periods	Drug: Placebo - Solution; Administered orally as solution; Drug: Placebo - Capsule; Administered orally as a capsule

Outcome Measures

Primary Outcome Measures :

1. Wake After Sleep Onset (WASO) With LY2624803 Compared to Placebo [ Time Frame: 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 :

1. Latency to Persistent Sleep (LPS) [ Time Frame: 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.
2. Total Sleep Time (TST) [ Time Frame: 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.
3. PK: Maximum Plasma Concentration (Cmax) of LY2624803 After Single Oral Dose in Period 4 [ Time Frame: 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 ]
4. PK: Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)] of LY2624803 After Single Oral Dose in Period 4 [ Time Frame: 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 ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

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

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

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01784614
• Other Study ID Numbers: 12662; I2K-JE-ZZAW ( Other Identifier: Eli Lilly and Company )
• First Posted: February 6, 2013
• Results First Posted: January 28, 2016
• Last Update Posted: January 28, 2016
• Last Verified: December 2015

Additional relevant MeSH terms:

Sleep Initiation and Maintenance Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Pharmaceutical Solutions