Clinical Trial 43869

Atlanta, GA 30328


Summary:

To evaluate the safety and tolerability of administering a single IV infusion dose of TAK-925 to patients with IH


Criteria:
  • Males and females aged 18 to 75 years old, inclusive, at the time of informed consent.
  • A diagnosis of IH, as defined by the ICSD-3 (Appendix E) as verified by medical records.
  • Onset of hypersomnia between 10 and 30 years of age.
  • Baseline polysomnogram (PSG) recording shows sleep efficiency >85%, total sleep time ≥6 hours, microarousals index <15/hour, periodic limb movement index associated with microarousals <10/hour.
  • NPSG demonstrates that subject does not have other comorbid sleep disorders or clinically significant nocturnal hypoxemia (oxygen saturation ≤80% for ≥5% of total sleep time) and that their AHI is ≤10.
  • Average (of 4 trials) baseline MWT sleep latency is less than or equal to 20 minutes and no single session has a sleep latency of greater than 30 minutes as determined by the site investigator.
  • Understand and be willing and able to comply with all study procedures and restrictions, and agree to participate by providing written informed consent.
  • Participants taking medication for treatment of EDS must be willing to discontinue medication prior to randomization into the study.
  • Body mass index (BMI) of 18 to 38.5 kg/m2 inclusive.
  • ESS score ≥11 at screening.
  • For a male subject who is nonsterilized and sexually active with a female partner of childbearing potential, the subject must meet the following birth control requirements: • Agrees to use an appropriate method of contraception, including a condom with or without spermicidal cream or jelly, from the first dose of study drug until 5 half-lives (1 day) plus 90 days after the last dose of study drug. No restrictions are required for a vasectomized male subject, provided the subject is at least 1-year post bilateral vasectomy procedure prior to the first dose of study drug. A male subject whose vasectomy procedure was performed less than 1 year prior to the first dose of study drug must follow the same restrictions as a non-vasectomized man. Appropriate documentation of surgical procedure should be provided. • Agrees to not donate sperm from the first dose of study drug until 5 half-lives plus 90 days after the last dose of study drug.
  • For a female subject of childbearing potential who is sexually active with a nonsterilized male partner, the subject must agree to use highly effective methods of contraception from signing of informed consent until 5 half-lives of TAK-925 (1 day) plus 30 days. Definitions and procedures for adequate contraception, pregnancy avoidance, and reporting responsibilities are defined in Appendix F.
  • For female subjects to be classified as “not of childbearing potential”, the subject must meet 1 of the following requirements: • Postmenopausal (defined as 12 months of spontaneous amenorrhea in females aged >45 years or 6 months of spontaneous amenorrhea in females aged >45 years, with serum follicle-stimulating hormone [FSH] levels >40 mIU/mL). • Surgically sterile by hysterectomy and/or bilateral oophorectomy with appropriate documentation of surgical procedure. • Had a tubal ligation with appropriate documentation of surgical procedure. • Has a congenital condition resulting in no uterus.
  • Female subjects of childbearing potential must have a negative urine pregnancy test at screening and Study Day -2 visits.
  • The subject must be normotensive, with no history of hypertension or use of antihypertensive medication. BP must be <140 mmHg (systolic) and <90 mmHg (diastolic). BP measures should be obtained after the subject has been resting for a minimum of 10 minutes and may be repeated 3 times if the BP is slightly elevated above these parameters. The lowest BP obtained may be used.


Exclusion Criteria
Any subject who meets any of the following criteria will not qualify for entry into the study:
  • Actigraphy obtained the week prior to NPSG at Study Day -2 Visit shows an average sleep duration of <420 minutes.
  • Patients on 300 mg of venlafaxine per day.
  • Positive urine screen for drugs of abuse and/or positive alcohol test at screening and Study Day -2. An exception at screening is made for stimulants or other drugs that the patient has been prescribed, but the drug screen must be negative at baseline.
  • History of drug or alcohol abuse within the 12 months prior to screening (Diagnostic and Statistical Manual of Mental Disorders, Edition 5 [DSM-5 criteria])5. Females who are pregnant or breastfeeding.
  • During screening, the subject has a resting HR outside of the range of 45 to 100 beats per minute, confirmed on repeat testing within a maximum of 30 minutes.
  • Screening ECG reveals a QT interval with Fridericia correction method >450 ms (men) or >470 ms (women).
  • Usual bedtime later than 01:00 or an occupation requiring nighttime shift work or variable shift work within the past 6 months or travel with significant jet lag within 14 days before Study Day -2. 9. Has medical disorder other than IH or has a history, based on interviews at the screening visit, of OSA or restless legs syndrome (RLS) confirmed by prior PSG data (such as AHI>10, periodic leg movements of sleep >15).
  • Use of any over-the-counter (OTC) or prescription medications with stimulating properties within 7 days prior to dosing or 5 half-lives (whichever is longer) that could affect the evaluation of EDS or use of sodium oxybate within 3 months of screening (see Table 7.a).
  • Nicotine dependence that is likely to have an effect on sleep (eg, a subject who routinely awakens at night to smoke) and/or unwilling to discontinue all smoking and nicotine use during the study.
  • Caffeine consumption of more than 600 mg/day for 7 days before Study Day 1 (1 serving of coffee is approximately equivalent to 120 mg of caffeine).
  • History or presence of any actual unstable medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or surgical history that could affect the safety of the subject or interfere with study efficacy, safety, PK assessments, or the ability of the subject to complete the trial per the judgment of the Investigator.
  • Employees or family members of the investigator, study site, contract research organization (CRO), or sponsor.
  • Subjects who have previously participated in an TAK-925 study or have participated in another investigational study within 4 weeks prior to the screening visit.
  • Subjects who, in the opinion of the clinical investigator, should not participate in the study.
  • Allergic to any excipient in the study drugs.
  • Has past or current history of epilepsy or seizures, including having had a single seizure or a history of childhood febrile seizures or has a clinically significant history of head trauma.
  • The subject has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency antibody/antigen, at the screening visit. Note: Subjects with positive hepatitis B virus or hepatitis C virus serology may be enrolled if quantitative polymerase chain reaction for hepatitis B virus or hepatitis C virus ribonucleic acid is negative20. Donated blood or plasma within 6 weeks prior to Study Day 1 or planning to donate blood or plasma within 12 weeks after study exit.
  • Answered “YES” on Questions 4 or 5 on the Suicidal Ideation subscale of the C-SSRS at Screening (defined period as 3 months prior to screening) or evidence of suicidal behavior within 6 months of screening as measured by the Suicidal Behavior subscale of the C-SSRS.
  • Recent history of a major depressive disorder (DSM-5), Beck depression inventory >16 and/or item G >0 at the screening visit.
  • Renal creatinine clearance ≤50 mL/min at the time of screening and Study Day -2.
  • Has a history of cerebral ischemia, transient ischemic attack, intracranial aneurysm, or arteriovenous malformation.
  • Has known coronary artery disease, a history of myocardial infarction, angina, cardiac rhythm abnormality, or heart failure.
  • The subject has abnormal laboratory test values that suggest a clinically significant underlying disease or any subject with transaminase (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) >2 ×upper limit of normal (ULN) at the screening visit or Study Day -2.


Qualified Participants May Receive:

Will receive compensation for time and travel for all completed study visits.


Clinical trials are medical research studies designed to test the safety and/or effectiveness of new investigational drugs, devices, or treatments in humans. These studies are conducted worldwide for a range of conditions and illnesses. Learn more about clinical research and participating in a study at About Clinical Trials.