MW151-101: First-in-human Study of MW151
Condition: Drug Toxicity
MeSH terms: Drug-Related Side Effects and Adverse Reactions
Intervention: Placebo; MW151, 10mg; MW151, 20mg; MW151, 40mg; MW151, 80mg; MW151, 160mg
Intervention description: Matched placebo administered orally; 10 mg MW151, 1 x 10mg capsule administered orally; 20 mg MW151, 1 x 20mg capsule administered orally; 40 mg MW151, 2 x 20mg capsule administered orally; 80 mg MW151, 1 x 80mg capsule administered orally; 160 mg MW151, 2 x 80mg capsule administered orally
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Dose-escalation study.
Masking: Single (Outcomes Assessor)
Masking description: Data from cohorts will be reviewed in a blinded manner.
Enrollment: 40.0
Sex: Female
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: cognitive disorder; pharmacokinetics; MW151; MW01-2-151SRM; PK; dose escalation

Summary:

      MW01-2-151SRM (=MW151), a small molecule, is being developed for the treatment of cognitive
      disorders. The development program is based on nonclinical evidence that MW151 improves
      neurocognitive outcomes in animal models of radiation-induced cognitive impairment,
      Alzheimer's disease, and other central nervous system (CNS) disorders.

      The present study will provide safety and pharmacokinetic (PK) information on single
      ascending doses to support decisions for continued clinical development.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to provide written informed consent

          -  In good health as determined by medical history, physical exam, laboratory
             examinations, ECG, and vital signs.

          -  Weight >50kg

          -  BMI <34 kg/m2.

          -  ECG without clinically significant pathologic abnormalities and with QTcF <450 ms -

          -  Systolic BP ≤ 150 mmHg and diastolic BP ≤ 90 mmHg at screening

          -  No suicidal ideation, as demonstrated by a score of "0" on the Columbia Suicide
             Severity Rating Scale (C-SSRS).

          -  Women who are neither pregnant (negative pregnancy test) nor nursing, and are either:
             surgically sterile, postmenopausal with last natural menses greater than 24 months, or
             premenopausal and agrees to use and acceptable form of birth control during the study
             and for 1 month after dosing.

          -  Adequate venous access for blood draws.

        Exclusion Criteria:

          -  Any unstable chronic medical condition requiring interventional treatment that might
             increase the risk to the subject or confound interpretation of safety observations.
             Subjects who are considered stable and who have been receiving stable treatment for
             medical condition for > 3 months may be considered with approval of medical monitor.

          -  Evidence of active infection requiring antibiotic therapy within 14 days prior to
             dosing.

          -  Medical history of vasculitis or any autoimmune disease excluding seasonal allergic
             rhinitis and childhood history of atopic dermatitis.

          -  History of any treatment for cancer within the past 2 years, other than basal cell or
             squamous cell carcinoma of the skin.

          -  Seropositive for human immunodeficiency virus (HIV).

          -  History of acute/chronic hepatitis B or C and/or carriers of hepatitis B

          -  Clinically significant abnormalities in screening laboratory tests

          -  Over-the-counter and herbal medications are prohibited within 10 days prior to study
             dosing (with exception of calcium/vitamin D supplements and ocular medications at the
             discretion of the Investigator). Stable doses (> to 3 months of stable dose) of
             prescription medications are allowed with the approval of the medical monitor (birth
             control medications are allowed without medical monitor approval). Subjects should not
             be on non-steroidal anti-inflammatory drugs or immunosuppressive drugs within 10 days
             prior to dosing.

          -  Use of known CYP450 CYP1A2, CYP2D6 or CYP3A4 inhibitors or inducers within 14 days of
             dosing or planned use during the study.

          -  Use of an investigational drug, vaccine, device, or blood product within 3 months
             prior to dosing in this study.

          -  Any disorder that could interfere with the absorption, distribution, metabolism or
             excretion of drugs (e.g. small bowel disease, Crohn's disease, celiac disease, or
             liver disease.)

          -  Psychiatric history of current or past psychosis, bi-polar disorder, clinical
             depression, or anxiety disorder requiring chronic medication within the past 5 years.

          -  History of substance abuse including alcohol within the past 5 years.

          -  Smoker.

          -  Current substance or drug dependence confirmed by positive urine drug screen at
             screening visit or Day -1 admission.

          -  Current alcohol abuse confirmed by positive breathalyzer at screening visit or Day -1
             admission.

          -  History of serious head injury as determined by the site investigator or designee.

          -  Chronic kidney disease (defined as the presence of any degree of proteinuria on urine
             analysis and/or an eGFR of <60 ml/min using the MDRD formula).

          -  Any reason or opinion of the investigator that would prevent the subject from
             participation in the study.

          -  Inability to follow the instructions or an unwillingness to cooperate with study
             procedures.

          -  Has donated more than 500 mL of blood within the last month prior to dosing.