Stage 1* To assess the safety and tolerability of single-ascending-dose levels of IW-6463 when administered to healthy subjectsStage 2* To assess the safety and tolerability of multiple-ascending-dose levels of IW-6463 when administered to healthy…
ID
Source
Brief title
Condition
- Mental impairment disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Stage 1
* Number of subjects with treatmentemergent adverse events (TEAEs) in the
IW-6463 dose-level cohorts vs the (pooled) placebo group.
Stage 2
* Number of subjects with TEAEs in the IW-6463 dose-level cohorts vs the
(pooled) placebo group.
Stage 3
* Number of subjects with TEAEs in the fed vs fasted dosing period.
* Plasma concentration of IW-6463 after single-dose administration under fed vs
fasted conditions.
Secondary outcome
Not applicable
Background summary
Dementia and cognitive impairment are large and growing health problems in
developed and developing countries.A therapeutic intervention that attenuates
cognitive decline, or preserves a patient*s current cognitive and functional
capacities, or improves either cognitive or functional
capacities, would be of great benefit for patients and their families and
caregivers. This study is being conducted to investigate the viability of
developing IW-6463 as a potential therapy in patients. As described in the
IW-6463 IB, nonclinical data suggest that IW-6463 may offer a novel approach to
potentially improve some of the deficits associated with various forms of
dementia.
Study objective
Stage 1
* To assess the safety and tolerability of single-ascending-dose levels of
IW-6463 when administered to healthy subjects
Stage 2
* To assess the safety and tolerability of multiple-ascending-dose levels of
IW-6463 when administered to healthy subjects for up to 14 days
Stage 3
* To assess the safety and tolerability of a single dose of IW-6463 when
administered to healthy subjects in fed vs fasted states.
* To explore the effects of food on IW-6463 pharmacokinetics (PK)
Study design
* Stage 1 will evaluate single-ascending-dose levels of study drug (ie, IW-6463
or placebo) in healthy adults using a randomized, double-blind,
sequential-group design.
* Stage 2 will evaluate multiple-ascending-dose levels (1 dose level per
cohort) of study drug administered to healthy adults (*65 years) for up to 14
days using a randomized, double-blind, sequential-group design.
* Stage 3 will investigate the effect of food on IW-6463 PK by administering a
single dose to healthy adults using an open-label, randomized, 2-period,
2-treatment (fed vs fasted conditions), crossover design.
Intervention
* Orally administered IW-6463 Tablets at doses ranging from 0.3 mg/day to not
more than 50 mg/day
* Orally administered Placebo to Match IW-6463 Tablets
Study burden and risks
Healthy subjects will be included in this study. No clinical benefit is to be
expected for these participants. The subjects will, however, receive financial
compensation. As Study C6463-101 represents the FIH study of IW-6463, the
safety profile of IW-6463 in
humans is not known. Nonclinical data indicate that the risk of IW-6463 to
human subjects is low when administered at the dose levels planned for this
study. Information regarding the potential benefits and risks and reasonably
expected treatment-emergent adverse events (TEAEs)
based on nonclinical data can be found in the IW-6463 IB. To minimize risk to
subjects, sentinel dosing will be utilized in Stage 1 in which the first
2 subjects (1 randomized to IW-6463 and 1 to placebo) in Cohorts 1 and 2 will
be dosed *24 hours in advance of the remaining subjects in the respective
cohort. Dosing of the remaining subjects within the respective cohort will
proceed (5 to IW-6463; 1 to placebo) on the basis that
no adverse events (AEs) of concern are reported (eg, serious adverse events
[SAEs] and/or severe AEs considered related to study drug), according to the
judgment of the Investigator and the Sponsor Medical Monitor. Dosing in each
subsequent dose-level cohort will
proceed sequentially after a safety review of the preceding cohort(s) has been
conducted by the Trial Safety Committee. This FIH stage in healthy volunteers
will provide safety, tolerability, and PK data pertaining to oral
administration of IW-6463 in the fasted versus fed states. These data will
inform key dosing instructions for future studies and, depending on the
results, will guide the dosing regarding food in future trials.
Binney Street 301
Cambridge Massachusetts MA 02142
US
Binney Street 301
Cambridge Massachusetts MA 02142
US
Listed location countries
Age
Inclusion criteria
1. Signed an ICF before any study-specific procedures are performed.
2. Age is *18 and <65 years at the Screening Visit.
3. Body mass index is *18.5 and <32 kg/m2 at the Screening Visit.
4. Ambulatory, in good health and no clinically significant findings on a
physical examination,
12-lead ECG, alcohol breathalyzer, and clinical laboratory tests (ie, serum
chemistry,
hematology, coagulation, urine drug screen, and urinalysis) after signing the
ICF but before
receiving the dose of study drug.
5. Screening results are negative for the hepatitis panel (hepatitis B surface
antigen [HBsAg],
the antihepatitis C virus [HCV]), and the human immunodeficiency virus (HIV)
antibody.
Exclusion criteria
1. Participated in any clinical study or treated with any investigational drug
or device within 28 days prior to Screening.
2. Clinically significant manifestation of metabolic; hepatic; renal;
hematological; pulmonary; cardiovascular; gastrointestinal; endocrinological;
musculoskeletal; dermatological; urogenital; eye, ear, nose, and/or throat;
psychiatric (including history of clinical depression or suicidal ideation, any
cognitive impairment or dementia); or neurological disorder that, in
the opinion of the Investigator, precludes the subject from participating in
the study.
3. Lymphoma, leukemia, or any malignancy within the past 5 years. Exception:
Basal cell or squamous epithelial carcinomas of the skin that have been
resected with no evidence of
metastatic disease for 3 years.
4. Clinically significant hypersensitivity or allergy to any of the inactive
ingredients contained in the active or placebo drug products.
5. Active alcoholism or drug addiction during the 12 months before the
Screening Visit or has a positive urine drug screen or alcohol test (see
Section 8.1.7.2) at the Screening Visit or at
Check-in to the Study Center.
6. 12-lead ECG at the Screening Visit demonstrating severe bradycardia (HR <40
beats per minute) or average QT interval corrected for HR using Fridericia*s
formula (QTcF) *450 msec for men or *470 msec for women.
7. Family history of short QT syndrome or long QT syndrome.
8. Elevated levels (ie, >1.5× the upper limit of normal as defined by the
laboratory) at the Screening Visit or at Check-in of alanine aminotransferase,
aspartate aminotransferase, or
creatinine.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-003694-99-NL |
| ClinicalTrials.gov | NCT03856827 |
| CCMO | NL67677.056.18 |