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MW151-101: First-in-human Study of MW151

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ClinicalTrials.gov Identifier: NCT04120233
Recruitment Status : Recruiting
First Posted : October 9, 2019
Last Update Posted : February 9, 2021
Sponsor:
Collaborators:
Duke Clinical Research Institute
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Linda Van Eldik, University of Kentucky

Tracking Information
First Submitted Date  ICMJE October 7, 2019
First Posted Date  ICMJE October 9, 2019
Last Update Posted Date February 9, 2021
Actual Study Start Date  ICMJE October 22, 2019
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 7, 2019)
Percentage of participants experiencing drug-related serious adverse events. [ Time Frame: Seven days ]
Percentage of participants experiencing drug-related serious adverse events.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: October 7, 2019)
  • Maximum Drug Concentration (Cmax) [ Time Frame: Seven days ]
    Peak serum concentration of MW151.
  • Time to Maximum Drug Concentration (Tmax) [ Time Frame: Seven days ]
    Time required to reach the maximum serum concentration of MW151.
  • Overall Drug Exposure (AUC) [ Time Frame: Seven days ]
    Overall drug exposure (mg*h/L) determined by calculating the area under the curve (AUC) from a plasma drug concentration-time curve.
  • Drug Half-Life (T1/2) [ Time Frame: Seven days ]
    Time at which the concentration of MW151 is at half the maximum concentration.
  • Elimination Rate Constant (Kel) [ Time Frame: Seven days ]
    Fraction of MW151 eliminated per unit of time (mathematical determination).
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE MW151-101: First-in-human Study of MW151
Official Title  ICMJE A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to Healthy Volunteers
Brief 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.

Detailed Description

The primary objective of this trial is to assess the safety and tolerability of single ascending doses of MW151 when administered orally to healthy adults.

Subjects will be screened prior to inpatient admission. Subjects will be admitted to the inpatient clinic on the day prior to dosing (Day -1) and will remain in the unit until discharge on Day 3. A follow-up visit will be done on Day 7. A single dose of study drug or placebo will be administered on Day 1. Healthy adult female subjects will be randomly assigned to one of 5 dose cohorts (8 subjects each). Each subject will receive a single dose of MW151 (10-160mg) or placebo under fasted conditions.

Following a review of safety and tolerability data for the first 24 hours of dosing in each cohort (including reported adverse events (AEs), physical examination findings, clinical laboratory results, vital signs, and electrocardiograms (ECGs), the remaining 6 subjects will be randomized in a 5:1 ratio. Dosing of the remaining subjects in a cohort may proceed after review of sentinel subject safety data collected during the first 24 hours of dosing and determination that no stopping rules are met. The remaining subjects in each cohort will be dosed sequentially, not simultaneously.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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.
Primary Purpose: Other
Condition  ICMJE Drug Toxicity
Intervention  ICMJE
  • Drug: Placebo
    Matched placebo administered orally
  • Drug: MW151, 10mg
    10 mg MW151, 1 x 10mg capsule administered orally
  • Drug: MW151, 20mg
    20 mg MW151, 1 x 20mg capsule administered orally
  • Drug: MW151, 40mg
    40 mg MW151, 2 x 20mg capsule administered orally
  • Drug: MW151, 80mg
    80 mg MW151, 1 x 80mg capsule administered orally
  • Drug: MW151, 160mg
    160 mg MW151, 2 x 80mg capsule administered orally
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Participants will receive placebo.
    Intervention: Drug: Placebo
  • Experimental: Dose 1
    Participants will receive 10 mg of MW151.
    Intervention: Drug: MW151, 10mg
  • Experimental: Dose 2
    Participants will receive 20mg of MW151.
    Intervention: Drug: MW151, 20mg
  • Experimental: Dose 3
    Participants will receive 40mg of MW151.
    Intervention: Drug: MW151, 40mg
  • Experimental: Dose 4
    Participants will receive 80mg of MW151.
    Intervention: Drug: MW151, 80mg
  • Experimental: Dose 5
    Participants will receive 160mg of MW151.
    Intervention: Drug: MW151, 160mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 7, 2019)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 30, 2021
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Linda J Van Eldik, PhD 859-257-5566 linda.vaneldik@gmail.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04120233
Other Study ID Numbers  ICMJE Pro00103072, IND143222
R01AG061898 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: There is no plan to share IPD at this time.
Responsible Party Linda Van Eldik, University of Kentucky
Study Sponsor  ICMJE Linda Van Eldik
Collaborators  ICMJE
  • Duke Clinical Research Institute
  • National Institute on Aging (NIA)
Investigators  ICMJE
Principal Investigator: Linda J Van Eldik, PhD University of Kentucky
PRS Account University of Kentucky
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP