Overview

This blinded placebo-controlled study is designed to evaluate the safety, tolerability, and PK in healthy participants of a single- and multiple-doses (SAD and MAD) of a new investigational drug: NUV001

Eligibility

Inclusion Criteria:

        Participants must satisfy all the following inclusion criteria before being allowed to
        enter the study:
          1. Male or female 18 to 55 years of age inclusive, at screening.
          2. A body mass index (BMI) between 18.00 and 30.00 kg/m² inclusive and a body weight
             between 60 kg and 100 kg for males (inclusive), and 50 kg and 100 kg for females
             (inclusive).
          3. Healthy as determined by the investigator based on medical history, physical
             examination findings, clinical laboratory test results, and digital 12 lead ECG
             readings (all results should be normal or, if out of range, non-clinically significant
             as determined by the Investigator).
          4. Vital signs at Screening and Admission are within the following ranges:
               -  Systolic blood pressure 90-140 mmHg (inclusive);
               -  Diastolic blood pressure 50-90 mmHg (inclusive);
               -  Heart rate 40-100 beats per minute (inclusive);
               -  Oral temperature 36.0-37.5°C (inclusive);
          5. AST, ALT, and Total bilirubin are <1.5 x ULN Screening and Admission.
          6. Serum creatinine is <1.5 mg/dL and estimated glomerular filtration rate is ≥60
             mL/min/1.73 m2 based on Chronic Kidney Disease Epidemiology Collaboration at Screening
             and Admission.
          7. QTcF is ≤450 ms for males and ≤470 ms for females at Screening and Admission.
          8. Non-smoker and no use of tobacco or nicotine-containing products for 6 months prior to
             screening.
          9. Have a high probability for compliance with and completion of the study.
         10. Female participants of childbearing potential [meaning who are not either surgically
             sterile (bilateral tubal ligation/occlusion, bilateral salpingectomy, bilateral
             oophorectomy or hysterectomy) or post-menopausal (no spontaneous menstrual periods for
             at least two years), confirmed by serum follicle stimulating hormone [FSH] in
             post-menopausal range based on laboratory reference range, must commit to using a
             highly effective method of birth control and throughout the entire study and for 90
             days after last dose of study drug:
               1. Combined hormonal estrogen and progestogen-containing, or progestogen-only
                  hormonal contraception associated with inhibition of ovulation, started at least
                  4 weeks prior to the dosing and condom with spermicide for the male partner.
               2. Intrauterine device or intrauterine hormone-releasing system placed at least 4
                  weeks prior to the dosing, and condom with spermicide for the male partner.
               3. Simultaneous use of a diaphragm or cervical cap with intravaginally applied
                  spermicide and, for the male partner, a male condom with spermicide.
               4. Sterile male partner, i.e., vasectomized since at least 3 months before dosing.
               5. Female participants with same-sex or no partner (when in line with the preferred
                  and usual subject's lifestyle) must agree to use an acceptable form of birth
                  control for duration noted above if they were to become sexually active with a
                  male partner. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
                  post-ovulation methods) is not acceptable.
             NB: Surgically sterile women, if the surgery (bilateral tubal ligation/occlusion,
             bilateral salpingectomy, bilateral oophorectomy, or hysterectomy) was performed at
             least 3 months prior to dosing, and female participants who have same-sex sexual
             relations do not have to use contraception. If the surgery was performed less than 3
             months before dosing, the female subject will be considered a woman of childbearing
             potential (WOCBP).
         11. Male participants with a female partner of childbearing potential will be required to
             be vasectomized at least 3 months prior to screening or use a condom with spermicide
             throughout the duration of the study and for 90 days after last dose of study drug.
         12. Male participants with same-sex or no partner (when in line with the subject's
             preferred and usual lifestyle) must agree to use an acceptable form of birth control
             for duration noted above if they were to become sexually active with a female partner
             of childbearing potential.
         13. Agree to avoid sperm or egg donation during the study and for 90 days following last
             dose of study drug.
         14. Can provide a voluntary written informed consent to participate in the study prior to
             any initiation of study-related procedures.
         15. Participant is not subject to any of the following procedures: ward of court,
             trusteeship, supervision order.
        Exclusion Criteria:
        If any of the following exclusion criteria apply, the participant must not enter in the
        study:
        Medical History
          1. Any significant cardiovascular (e.g., heart failure), hepatic, renal, respiratory
             (e.g., asthma), gastrointestinal, endocrine (e.g., diabetes, dyslipidemia),
             immunologic, dermatological, hematological, neurologic, psychiatric disease or history
             of any clinically important drug allergy.
          2. Acute disease state (e.g., vomiting, fever, diarrhea) within 7 days before Day 1 of
             Treatment Period 1 (SAD).
          3. Pregnant or lactating female.
          4. Inability to follow study procedures.
          5. Use of recreational drugs within 1 year before Day 1 of Treatment Period 1 (SAD).
          6. History of alcoholism within 1 year before Day 1 of Treatment Period 1 and/or Regular
             alcohol consumption >14 units of alcohol per week (1 unit = ½ pint [approximately 240
             mL] beer, 25 mL of 40% spirit or a 125 mL glass of wine) within 3 months prior to the
             admission.
          7. Donation of blood or blood loss (i.e., > 400 mL) within 90 days before Day 1 of
             Treatment Period 1 (SAD).
          8. Known allergy or intolerance to study drug, or excipients present in drug product.
             Physical and Laboratory Findings
          9. Positive serologic findings for human immunodeficiency virus (HIV) antibodies,
             hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibody at
             Screening.
         10. Positive findings of urine drug screen [methadone, barbiturates, oxycodone,
             amphetamines, methamphetamines, opiates, cannabinoids, cocaine, benzodiazepines,
             tricyclic antidepressants (TCA), 3,4-methylenedioxy-methamphetamine (MDMA; ecstasy),
             phencyclidine, cotinine] at screening or admission.
         11. Positive Covid -19 by rapid antigen test at admission.
             Prohibited Treatments and study restrictions:
         12. Use of any investigational drug within 30 days before study drug administration on Day
             1 of Treatment Period 1 (SAD) except for medications needed to treat Adverse Events.
         13. Use of prescription or over the counter (OTC) medications, herbal supplements,
             antacids, vitamins, minerals or food supplements (especially those containing
             tryptophane, vitamin B3 (NAM and niacin)) within the previous 14 days or 5 half-lives
             (whichever is longer) before Day 1 of Treatment Period 1 (SAD) and throughout the
             study and follow-up visit (except for occasional use of nonsteroidal anti-inflammatory
             drugs (NSAIDs) or acetaminophen, and oral contraception for females of childbearing
             potential).
         14. Consumption of grapefruit juice, alcoholic beverages or any caffeine-containing
             products or stimulating beverages containing xanthine derivatives (e.g., coffee, tea,
             chocolate, or soda) for 48 hours prior to dosing on D1 until D2 (Treatment Period 1
             (SAD)) and for 48 hours prior to dosing on D1 until the end of the inpatient period
             (for Treatment Period (MAD)).
         15. Participants will be requested to abstain from strenuous physical activity, for 4 days
             prior to D1 of each treatment period (SAD/MAD), during confinement for each treatment
             period and 4 days prior to the follow up visit.