Healthy volunteers Other
Conditions
Interventions
Experimental Drug: JZP505
Control Drug: Placebo
A single-site, randomized (by computer), double-blind, single-ascending dose (SAD) and multiple-ascending dose (MAD) study of JZP505 will be conducted
Part B: MAD)
Dosing:
SAD: Single oral doses of JZP505 or placebo (150mg-2400mg)
Food Effect: Two single oral doses of JZP505 or placebo in fasted and fed states in Cohort A2 (300mg)
MAD: Once or twic
Sponsors
JAZZ Pharmaceuticals Research UK Ltd
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: Age 1. Is 18 to 55 years of age inclusive at the time of signing the informed consent Type of Participant and Disease Characteristics 2. Are overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring Weight 3. Has a minimum body weight of 50 kg and a BMI within the range 18.5 to 32 kg/m2, inclusive 4. Is male or female: 4.1. Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 90 days after the last dose of study intervention: 4.1.1. Refrain from donating sperm. PLUS either of the following: 4.1.2. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR 4.1.3. Use contraception/barrier as follows: 4.1.3.1. Use a male condom with female partner use of an additional highly effective contraceptive method with a failure rate of < 1% per year as described in Contraceptive and Barrier Requirements when having sexual intercourse with a WOCBP who is not currently pregnant 4.1.3.2. Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person 4.2. Female participants are eligible to participate if: 4.2.1. She is a WONCBP, as defined in Contraceptive and Barrier Guidance Informed Consent 5. Is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
Exclusion criteria
Exclusion criteria: Medical Conditions 1. Any history of suicidal behavior or any suicidal ideation, as indicated by a positive response to Item 4 or Item 5 on the C-SSRS, or past or current history of self-harm thoughts or actions as identified on C-SSRS at screening 2. Presence or history of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, as determined by the investigator (or designee); any known or suspected hypersensitivity to cannabinoids, or any of the excipients of JZP505. Hay fever is allowed unless it is active 3. Presence of congenital nonhemolytic hyperbilirubinemia (eg, Gilbert’s syndrome) at either screening or admission on Day –1, as assessed by the investigator (or designee) 4. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs 5. History of drug abuse within 2 years of screening or current habituation to any medications or illegal drugs 6. Any history of fits/seizures (apart from childhood febrile convulsions before the age of 6 years). Known or suspected history or family history of schizophrenia or other psychotic illness; history of severe personality disorder or other significant psychiatric disorder 7. Poor peripheral venous access 8. Clinically significant renal disease, nephrectomy, renal transplant or estimated glomerular filtration rate of 1.0 × ULN 13.2. TBL > ULN 13.3. INR > ULN 13.4. Serum creatinine > 1 × ULN 14. Hemoglobin level 140 mmHg) or a diastolic blood pressure of 90 mmHg), confirmed by repeat readings 17. Participants with an orthostatic decrease in systolic blood pressure > 20 mmHg, or a decrease in diastolic blood pressure >10 mmHg upon standing 18. Clinically significant ECG abnormality at screening (confirmed by repeat within 2 hours), including, but not limited to: 18.1. PR interval > 220 msec 18.2. QRS duration > 120 msec 18.3. Complete left or right bundle branch block, second- or third-degree heart block 18.4. QTcF > 450 msec for male participants or > 470 msec for female participants; the ECG may be repeated up to 2 times at the investigator’s discretion for confirmation (with 2 of 3 ECGs being below the threshold) 18.5. History of additional risk factors for torsade
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Part A: Incidence and severity of treatment-emergent adverse events (TEAEs) measured using the number of participants at Day 1 up to 9 months 2. Part A: Change in clinical laboratory test parameters measured using IU/L (International Units per Litre) at Day 2: 24 hours postdose; Day 4: 72 hours postdose 3. Part A: Changes in 12-lead electrocardiogram (ECG) parameters measured using milliseconds (ms) at Predose (Day 1) and 1, 2, 4, 8, 12, 24, and 72 hours postdose 4. Part A: Changes in vital sign measurements-supine blood pressure measured using mmHg at Day 1: predose and 1, 2, 4, 8 hours postdose; Day 2: 24 hours postdose; Day 3: 48 hours postdose; Day 4: 72 hours postdose 5. Part A: Changes in vital sign measurements-pulse rate measured using beats/min at Day 1: predose and 1, 2, 4, 8 hours postdose; Day 2: 24 hours postdose; Day 3: 48 hours postdose; Day 4: 72 hours postdose 6. Part A: Changes in vital sign measurements-respiratory rate measured using breaths/min at Day 1: predose and 1, 2, 4, 8 hours postdose; Day 2: 24 hours postdose; Day 3: 48 hours postdose; Day 4: 72 hours postdose 7. Part A: Changes in vital sign measurements-oral temperature measured using celcius (°C) at Day 1: predose and 1, 2, 4, 8 hours postdose; Day 2: 24 hours postdose; Day 3: 48 hours postdose; Day 4: 72 hours postdose 8. Part A: Changes in Columbia Suicide Severity Rating Scale (C-SSRS) Assessment measured using C-SSRS at Baseline and final visit 9. Part A: Maximum observed plasma concentration (Cmax) measured using ng/mL at Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours postdose 10. Part A: Area under the plasma concentration-time curve from time zero to the time of the final quantifiable concentration (AUCt) measured using h*ng/mL at Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours postdose 11. Part A: Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC8) measured u | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Part A: Dose proportionality of JZP505 for Cmax measured using ng/mL at Day 1 2. Part A: Dose proportionality of JZP505 for AUCt measured using h*ng/mL at Day 1 3. Part A: Dose proportionality of JZP505 for AUC8 measured using h*ng/mL at Day 1 4. Part A: Cumulative amount of unchanged drug excreted into the urine (Ae0-t) measured using mg at Day 1: Predose, 0-6, 6-12, 12-24, 24-48, and 48-72 hours postdose 5. Part A: The amount of drug excreted in urine as a percentage of administered dose (Fe %) measured using % at Day 1: Predose, 0-6, 6-12, 12-24, 24-48, and 48-72 hours postdose 6. Part A: Renal clearance (CLR) measured using L/h at Day 1: Predose, 0-6, 6-12, 12-24, 24-48, and 48-72 hours postdose 7. Part A: Change from Baseline in central nervous system (CNS)-related effects as determined by Bond-Lader VAS measured using mm at Day 1: predose and 2, 4, 8, and 12 hours postdose; Day 2: 24 hours postdose; Day 4: 72 hours postdose 8. Part A: Fed and fasted state Cmax following a single dose of JZP505 measured using ng/mL at Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours postdose 9. Part A: Fed and fasted state AUCt following a single dose of JZP505 measured using h*ng/mL at Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours postdose 10. Part A: Fed and fasted state AUC8 following a single dose of JZP505 measured using h*ng/mL at Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours postdose 11. Part A: Incidence and severity of TEAEs in fed and fasted state measured using number of participants at Day 1 up to 9 months 12. Part A: Change in clinical laboratory test parameters in fed and fasted State measured using IU/L at Day 2: 24 hours postdose; Day 4: 72 hours postdose 13. Part A: Changes in 12-lead ECG parameters in fed and fasted State measured using ms at Predose (Day 1) and 1, 2, 4, 8, 12, 24, and 72 hours postdose 14. Part A: Changes in vital sign measurem | — |
Countries
England, United Kingdom
Contacts
Public Contact- Clinical Trial Disclosure and Transparency
Outcome results
None listed