Drug ToxicityPhase 1NCT04120233
MW151-101: First-in-human Study of MW151
A Phase 1 study testing MW151, 10mg, MW151, 20mg and MW151, 40mg in people with Drug Toxicity, run by Linda Van Eldik at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Drug Toxicity
- What is being tested?
- MW151, 10mg, MW151, 20mg and MW151, 40mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Oct 2019to 16 Sep 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke Clinical Research Institute
Durham, North Carolina, 27705
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Drug Toxicity
- Being tested
- Placebo, MW151, 10mg, MW151, 20mg, MW151, 40mg, MW151, 80mg
- Keywords
- cognitive disorder, pharmacokinetics, MW151, MW01-2-151SRM, PK, dose escalation
- Medical subject headings
- Drug-Related Side Effects and Adverse Reactions, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Matched placebo administered orally
MW151, 10mgDrug
10 mg MW151, 1 x 10mg capsule administered orally
MW151, 20mgDrug
20 mg MW151, 1 x 20mg capsule administered orally
MW151, 40mgDrug
40 mg MW151, 2 x 20mg capsule administered orally
MW151, 80mgDrug
80 mg MW151, 1 x 80mg capsule administered orally
MW151, 160mgDrug
160 mg MW151, 2 x 80mg capsule administered orally
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants will receive placebo. Receives: Drug: Placebo |
| Dose 1 | Experimental | Participants will receive 10 mg of MW151. Receives: Drug: MW151, 10mg |
| Dose 2 | Experimental | Participants will receive 20mg of MW151. Receives: Drug: MW151, 20mg |
| Dose 3 | Experimental | Participants will receive 40mg of MW151. Receives: Drug: MW151, 40mg |
| Dose 4 | Experimental | Participants will receive 80mg of MW151. Receives: Drug: MW151, 80mg |
| Dose 5 | Experimental | Participants will receive 160mg of MW151. Receives: Drug: MW151, 160mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Seven days
Secondary outcomes (5)
Maximum Drug Concentration (Cmax)
Peak serum concentration of MW151.
Measured: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Time to Maximum Drug Concentration (Tmax)
Time required to reach the maximum serum concentration of MW151.
Measured: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Overall Drug Exposure (AUC)
Overall drug exposure (h*ng/mL) determined by calculating the area under the curve (AUC) from a plasma drug concentration-time curve.
Measured: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Drug Half-Life (T1/2)
Time at which the concentration of MW151 is at half the maximum concentration.
Measured: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Elimination Rate Constant (Kel)
Fraction of MW151 eliminated per unit of time (mathematical determination).
Measured: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2019
- Study start22 Oct 2019
- Primary completion16 Sep 2021
- Study completion16 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Drug ToxicityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Dose-escalation study.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Linda Van Eldik
- Sponsor type
- University, hospital or other
- Collaborators
- Duke Clinical Research Institute, National Institute on Aging (NIA)
- Responsible party
- Sponsor-investigator, Linda Van Eldik, University of Kentucky
- Investigators
- Linda J Van Eldik, PhD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04120233
- Sponsor's protocol ID
- Pro00103072, IND143222
- Other IDs
- R01AG061898
- Status last verified
- Dec 2022
- First submitted
- 7 Oct 2019
- Last updated
- 30 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share IPD at this time.
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04120233
- Acronym / sponsor ID
- Pro00103072, IND143222
- Conditions
- Drug Toxicity
- Keywords
- cognitive disorder, pharmacokinetics, MW151, MW01-2-151SRM, PK, dose escalation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Linda Van EldikUniversity, hospital or other
- Collaborators
- Duke Clinical Research Institute, National Institute on Aging (NIA)
- Study start
- 22 Oct 2019 (actual)
- Primary completion
- 16 Sep 2021 (actual)
- Study completion
- 16 Sep 2021 (actual)
- First posted
- 9 Oct 2019 (actual)
- Results
- Posted 30 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 6
- Model description
- Dose-escalation study.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive placebo. |
| Dose 1 | Experimental | Drug: MW151, 10mgParticipants will receive 10 mg of MW151. |
| Dose 2 | Experimental | Drug: MW151, 20mgParticipants will receive 20mg of MW151. |
| Dose 3 | Experimental | Drug: MW151, 40mgParticipants will receive 40mg of MW151. |
| Dose 4 | Experimental | Drug: MW151, 80mgParticipants will receive 80mg of MW151. |
| Dose 5 | Experimental | Drug: MW151, 160mgParticipants will receive 160mg of MW151. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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 -
Key exclusion criteria (21 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboMatched placebo administered orally | Drug | Placebo |
| MW151, 10mg10 mg MW151, 1 x 10mg capsule administered orally | Drug | Dose 1 |
| MW151, 20mg20 mg MW151, 1 x 20mg capsule administered orally | Drug | Dose 2 |
| MW151, 40mg40 mg MW151, 2 x 20mg capsule administered orally | Drug | Dose 3 |
| MW151, 80mg80 mg MW151, 1 x 80mg capsule administered orally | Drug | Dose 4 |
| MW151, 160mg160 mg MW151, 2 x 80mg capsule administered orally | Drug | Dose 5 |
Primary outcome
Percentage of Participants Experiencing Drug-related Serious Adverse Events.
Time frame: Seven days
Percentage of participants experiencing drug-related serious adverse events from the start of study drug administration up to 7-day follow-up.
5 secondary outcomes
Maximum Drug Concentration (Cmax)
Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Time to Maximum Drug Concentration (Tmax)
Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Overall Drug Exposure (AUC)
Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Drug Half-Life (T1/2)
Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Elimination Rate Constant (Kel)
Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. There is no plan to share IPD at this time.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Linda J Van Eldik, PhD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MW151, 10mg, MW151, 20mg and MW151, 40mg in people with Drug Toxicity, run by Linda Van Eldik at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Experiencing Drug-related Serious Adverse Events. (time frame: Seven days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2022.