Cognitive Dysfunction, Schizophrenia
Conditions
Brief summary
This first-in-human clinical trial with a randomized, double-blind, placebo-controlled, dose-escalation study design is regarded as standard to test the safety, tolerability, and pharmacokinetics of KYN-5356. The study comprises 3 parts: Part 1: Single Ascending Dose study Part 2: Multiple Ascending Dose study Part 3: Food Effect study The aim of Parts 1 and 2 of the study is to evaluate the safety and tolerability following single and multiple ascending doses of KYN-5356. The secondary aim is to evaluate the pharmacokinetics (PK) of escalating single and multiple doses of KYN-5356. In Part 2, cerebrospinal fluid will be sampled to explore PK and pharmacodynamic effects of KYN-5356. The potential effect of food intake on the disposition of KYN-5356 following a single oral dose will be evaluated in Part 3. Part 3 is an open-label, randomized, 2 period, 2 sequence design.
Interventions
DRUGplacebo
placebo, oral tablet
DRUGKYN-5356
KYN-5356, oral tablet
Sponsors
Parexel
Kynexis B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject understands the study procedures and agrees to participate by providing written informed consent prior to any study procedures. * Subject is between 18 and 55 years of age (inclusive), on the date of signing the informed consent form. * Subject has a body mass index between 18 and 30 kg/m2, inclusive. * A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential or a woman of childbearing potential who agrees to follow the contraceptive guidance (highly effective birth control method) from Screening until end of the study. Note: Males should use appropriate contraceptive method from Screening until end of the study. * Subject is judged to be in good health by the Principal Investigator based upon the results of a medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory safety tests. * Subject is willing to adhere to the study requirements and restrictions.
Exclusion criteria
* Subject has positive serology for HBsAg, HCV, or HIV, or history of hepatitis from any cause with the exception of hepatitis A that was resolved at least 3 months prior to first dosing of the Investigational Medicinal Product. * Subject has any illness judged by the Principal Investigator as clinically significant, in the 3 months prior to first dosing of the Investigational Medicinal Product. * Subject has a suicidality score of yes on item 4 or item 5 of the suicidal ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or yes on any item of the suicidal behavior section, except for the Non-Suicidal Self-Injurious Behavior (item also included in the suicidal behavior section), if this behavior occurred in the past 2 years. * Subject has a history or current sign or symptom of psychiatric or neurologic disease. * Subject has a history of head trauma in the past year and/or current seizures. * Subject is a smoker (use of tobacco products in the previous 3 months from Screening) or uses nicotine or nicotine-containing products and has a positive urine cotinine test at Screening or Admission. * Subject has a history of alcohol and/or illicit drug abuse within 2 years of entry or has a positive screening test for alcohol and/or drugs of abuse at Screening or Admission. * Subject consumes caffeine containing beverages exceeding 500 mg caffeine per day (5 cups of coffee) during the off-site days during the study. * Subject has regular excessive consumption of alcohol within 6 months prior to Screening (7 drinks/week for females, 14 drinks/week for males where 1 drink = 150 mL of wine or 360 mL of beer or 45 mL of hard liquor). * Subject has a history or current sign or symptom of a cardiovascular, renal, or metabolic bone disease or disease of bone remodeling, or any history of endocrine disease, including an abnormal laboratory result for pre-specified clinical laboratory safety parameters related to these conditions. * Subject has a history or presence of clinically significant abnormalities detected on 12-lead ECG of either rhythm or conduction. A first-degree atrioventricular block will not be considered as a significant abnormality. Subject has QTcF \> 450 ms (mean values per parameter will be considered) detected on the 12-lead ECG at Screening or Admission. * Presence or sequelae of gastrointestinal, liver, kidney (creatinine clearance \<85 mL/min, using the Cockcroft-Gault formula), or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs at Screening or Admission. * Subject has a history of malignancy within the past 5 years prior to Screening with the exception of excised and curatively treated non-metastatic cell carcinoma of the skin which is considered cured with minimal risk of recurrence. * Subject tests positive for SARS-CoV-2 at Admission. * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Emergent Adverse Events | Initiation of dosing through the last follow-up visit after the last dose, approximately 8 days in the MAD and 5 days after dosing in the SAD and the Food Effect parts of the study | All cohorts |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters: tmax [SAD] | Baseline (predose) through 72 hours post dosing | Time of maximum plasma concentration determined directly from the concentration-time profile. For each dose in SAD part. |
| PK parameters: AUCinf [SAD] | Baseline (predose) through 72 hours post dosing | Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time calculated using the linear-log trapezoidal rule. For each dose in SAD part. |
| PK parameters: Cmax on Day 1 [MAD] | Baseline (predose) through 24 hours post first dosing | Maximum plasma concentration determined directly from the concentration-time profile. For each dose in MAD part |
| PK parameters: tmax on Day 1 [MAD] | Baseline (predose) through 24 hours post first dosing | Time of maximum plasma concentration determined directly from the concentration-time profile. For each dose in MAD part. |
| PK parameters: Cmax [SAD] | Baseline (predose) through 72 hours post dosing | Maximum plasma concentration determined directly from the concentration-time profile. For each dose in SAD part. |
| PK parameters: tmax,ss [MAD] | Baseline (predose) through 96 hours post dosing on Day 7. | Time of maximum plasma concentration determined directly from the concentration-time profile at steady state. For each dose in MAD part. |
| PK parameters: AUCtau on Days 1 and 7 [MAD] | Baseline (predose) through 96 hours post dosing on Day 7. | Area under the concentration-time curve over the dosing interval. For each dose in MAD part |
| PK parameters: AUCinf [MAD] | Baseline (predose) through 96 hours post dosing on Day 7. | Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time calculated using the linear-log trapezoidal rule. For each dose in MAD part. |
| PK parameters: Cmax,ss [MAD] | Baseline (predose) through 96 hours post dosing on Day 7. | Maximum observed plasma concentration during a dosing interval at steady state. For each dose in MAD part. |
Countries
United States
Outcome results
None listed