Healthy Volunteers
Conditions
Keywords
Phase 1, Single ascending dose (SAD), Multiple ascending dose (MAD), Safety, Tolerance, Pharmacokinetics
Brief summary
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
Detailed description
This is a phase I, single-center, double blind, randomized, single- and multiple-dose, study in four (4) cohorts of eight (8) healthy adult male and female participants per period and dose level. This 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 The study will consist of a screening period up to 28 days followed by two (2) treatment periods per participant: * Treatment Period 1: Single ascending dose (SAD) part with a 3-days inpatient period. * Treatment Period 2: Multiple ascending dose (MAD) part with a 16-days inpatient period. Dosing from Period 2 Day 1 to Day 14. A washout of at least 5 days after the first dosing (Period 1 Day 1) should take place between the two periods. A follow-up visit will take place between 6 to 10 days after last dosing (i.e., D14 in period 2) or early discontinuation. NUV001 will be given orally at four dose levels. Each participant will undergo two treatment periods, but they will receive only one dose level. The decision to proceed to subsequent dosing cohorts will be made based on a blinded review of the emerging safety data and available PK data.
Interventions
DRUGNUV001 active cohort 1
6 participants will be assigned to receive active treatment
DRUGNUV001 active cohort 2
6 participants will be assigned to receive active treatment
DRUGNUV001 active cohort 3
6 participants will be assigned to receive active treatment
DRUGNUV001 active cohort 4
6 participants will be assigned to receive active treatment
DRUGNUV001 placebo cohort 1
2 participants will be assigned to receive placebo
DRUGNUV001 placebo cohort 2
2 participants will be assigned to receive placebo
DRUGNUV001 placebo cohort 3
2 participants will be assigned to receive placebo
DRUGNUV001 placebo cohort 4
2 participants will be assigned to receive placebo
Sponsors
Medpace, Inc.
LGD
Anapharm
Nuvamid SA
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety as measured by subject incidence of treatment-emergent adverse events (SAD/MAD) | SAD: First dose date (treatment period 1 Day 1) plus 1 day (until discharge), MAD: First dose date (treatment period 2 Day 1) up to discharge (treatment period 2 Day 15) plus 10 days (follow up visit). | Percentage of Participants Who Experienced Any Adverse Events. |
| Safety as measured by subject incidence of treatment-emergent clinically significant changes in vital signs (SAD/MAD) | SAD: First admission (treatment period 1 Day -1) until discharge (treatment period 1 Day 2); MAD: Second admission (treatment period 2 Day -1) up to discharge (treatment period 2 Day 15) plus 10 days (follow up visit). | Subject incidence of treatment-emergent clinically significant changes in vital signs (Systolic and Diastolic Blood Pressure in millimeters of mercury (mmHg), Heart Rate in beats per minute (bpm), and Oral Body temperature in Celsius). |
| Safety as measured by subject incidence of treatment-emergent clinically significant changes in Electrocardiograms (SAD/MAD) | SAD: First admission (treatment period 1 Day -1) until discharge (treatment period 1 Day 2); MAD: Second admission (treatment period 2 Day -1) up to discharge (treatment period 2 Day 15) plus 10 days (follow up visit). | Subject incidence of treatment-emergent clinically significant changes in 12-lead ECGs (PR interval in milliseconds (msec), QRS duration in milliseconds (msec), QRS axis in milliseconds (msec), QT interval in milliseconds (msec)). |
| Safety as measured by subject incidence of treatment-emergent clinically significant changes in Blood safety tests (SAD/MAD) | SAD: First admission (treatment period 1 Day -1) until discharge (treatment period 1 Day 2); MAD: Second admission (treatment period 2 Day -1) up to discharge (treatment period 2 Day 15) plus 10 days (follow up visit). | Subject incidence of treatment-emergent clinically significant changes in clinical laboratory safety tests (Complete Blood Count (absolute counts and %), Fasting blood glucose concentration and Serum concentrations in Electrolytes, Protein, Albumin, Total Bilirubin, Blood urea nitrogen, Creatinine, Aspartate Aminotransferase, Alanine Aminotransferase, estimated Glomerular Filtration Rate (eGFR using CKD EPI equation, Activated partial thromboplastin time (aPTT) and Prothrombin Time test (PT) with International Normalized Ratio (INR)). |
| Safety as measured by subject incidence of treatment-emergent clinically significant changes in Urinalysis safety tests (SAD/MAD) | SAD: First admission (treatment period 1 Day -1) until discharge (treatment period 1 Day 2); MAD: Second admission (treatment period 2 Day -1) up to discharge (treatment period 2 Day 15) plus 10 days (follow up visit). | Subject incidence of treatment-emergent clinically significant changes in Urinalysis safety tests (pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte esterase). |
| Safety as measured by subject incidence of treatment-emergent clinically significant changes in Weight (SAD/MAD) | SAD: First admission (treatment period 1 Day -1) until discharge (treatment period 1 Day 2); MAD: Second admission (treatment period 2 Day -1) up to discharge (treatment period 2 Day 15) plus 10 days (follow up visit). | Subject incidence of treatment-emergent clinically significant changes in Weight in kilograms (Kg). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NUV001 concentration in whole blood (SAD/MAD) | Treatment period 1 (SAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Day 1; Treatment period 2 (MAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Days 1 and 14 and Predose on Days 4, 8 and 12 | Evolution from baseline of NUV001 concentration in whole blood |
| NUV001 metabolite A concentration in whole blood (SAD/MAD) | Treatment period 1 (SAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Day 1; Treatment period 2 (MAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Days 1 and 14 and Predose on Days 4, 8 and 12 | Evolution from baseline of NUV001 metabolite A concentration in whole blood |
| NUV001 metabolite B concentration in plasma (SAD/MAD) | Treatment period 1 (SAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Day 1; Treatment period 2 (MAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Days 1 and 14 and Predose on Days 4, 8 and 12 | Evolution from baseline of NUV001 metabolite B concentration in plasma |
| NUV001 metabolite C concentration in plasma (SAD/MAD) | Treatment period 1 (SAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Day 1; Treatment period 2 (MAD) : Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after dosing on Days 1 and 14 and Predose on Days 4, 8 and 12 | Evolution from baseline of NUV001 metabolite C concentration in plasma |
| NUV001 metabolite C concentration in urine (SAD/MAD) | Treatment period 1 (SAD) : collection at Predose and during intervals 0-6, 6-12 and 12-24 hours on Day 1 ; Treatment period 2 (MAD) : collection at Predose and during intervals 0-6, 6-12 and 12-24 hours on Days 1 and 14 | Evolution from baseline of NUV001 metabolite C concentration in urine |
| NUV001 metabolite D concentration in urine (SAD/MAD) | Treatment period 1 (SAD) : collection at Predose and during intervals 0-6, 6-12 and 12-24 hours on Day 1 ; Treatment period 2 (MAD) : collection at Predose and during intervals 0-6, 6-12 and 12-24 hours on Days 1 and 14 | Evolution from baseline of NUV001 metabolite D concentration in urine |
Countries
United States
Outcome results
None listed