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

NCT04120233 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: Pro00103072, IND143222R01AG061898
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug Toxicity

Keywords

cognitive disorder; pharmacokinetics; MW151; MW01-2-151SRM; PK; dose escalation

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Experiencing Drug-related Serious Adverse Events.

  Percentage of participants experiencing drug-related serious adverse events from the start of study drug administration up to 7-day follow-up.

  Seven days

Secondary Outcomes (5)

• Maximum Drug Concentration (Cmax)

  predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose

• Time to Maximum Drug Concentration (Tmax)

  predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose

• Overall Drug Exposure (AUC)

  predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose

• Drug Half-Life (T1/2)

  predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose

• Elimination Rate Constant (Kel)

  predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose

Study Arms (6)

Placebo

PLACEBO COMPARATOR

Participants will receive placebo.

Drug: Placebo

Dose 1

EXPERIMENTAL

Participants will receive 10 mg of MW151.

Drug: MW151, 10mg

Dose 2

EXPERIMENTAL

Participants will receive 20mg of MW151.

Drug: MW151, 20mg

Dose 3

EXPERIMENTAL

Participants will receive 40mg of MW151.

Drug: MW151, 40mg

Dose 4

EXPERIMENTAL

Participants will receive 80mg of MW151.

Drug: MW151, 80mg

Dose 5

EXPERIMENTAL

Participants will receive 160mg of MW151.

Drug: MW151, 160mg

Interventions

Placebo DRUG

Matched placebo administered orally

Placebo

MW151, 10mg DRUG

10 mg MW151, 1 x 10mg capsule administered orally

Dose 1

MW151, 20mg DRUG

20 mg MW151, 1 x 20mg capsule administered orally

Dose 2

MW151, 40mg DRUG

40 mg MW151, 2 x 20mg capsule administered orally

Dose 3

MW151, 80mg DRUG

80 mg MW151, 1 x 80mg capsule administered orally

Dose 4

MW151, 160mg DRUG

160 mg MW151, 2 x 80mg capsule administered orally

Dose 5

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Linda Van Eldik: lead
• Duke Clinical Research Institute: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Duke Clinical Research Institute

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions; Cognitive Dysfunction

Interventions

2-(4-(4-methyl-6-phenylpyridazin-3-yl)piperazin-1-yl)pyrimidine

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Linda J. Van Eldik
• Organization: University of Kentucky

linda.vaneldik@uky.edu

1-859-257-5566

Study Officials

• Linda J Van Eldik, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Data from cohorts will be reviewed in a blinded manner.
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Sanders-Brown Center on Aging

Model Details: Dose-escalation study.

Study Record Dates

• First Submitted: October 7, 2019
• First Posted: October 9, 2019
• Study Start: October 22, 2019
• Primary Completion: September 16, 2021
• Study Completion: September 16, 2021
• Last Updated: December 30, 2022
• Results First Posted: December 30, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)