Healthy participants Other
Conditions
Interventions
A single-dose study of orally administered PTC923 in 60 healthy adults (30 Japanese and 30 non-Japanese subjects) equally divided into 5 cohorts (20, 40 x2, and 60 mg x2/kg), each composed of 6 Japane
3 participants per sequence first receive 40 mg/kg of PTC923 in a fasted or fed (low-fat diet) state. After receiving their first dose of PTC923 in either a fed or fasted state, participants will ente
Sponsors
PTC Therapeutics (United States)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Males or females =18 and =55 years of age and have a BMI of =18.5 and =30.0 kg/m2 2. Participants must understand the nature of the study and must provide signed and dated written informed consent before the conduct of any study-related procedures. 3. Women of childbearing potential, as defined in (CTFG 2020), must have a negative pregnancy testing at Screening and agree to true abstinence (i.e., when this is in line with the preferred and usual lifestyle of the subject) or the use of barrier contraceptive (i.e., condom) in combination with at least one of the following highly effective forms of contraception (with a failure rate of <1% per year when used consistently and correctly) 4. Males with female partners of childbearing potential must agree to use barrier contraceptive (i.e., condom) and their female partners must use a highly effective method of contraception from Screening through 90 days after the last dose of study drug. Males must also refrain from sperm donations during this time period. Males who are abstinent will not be required to use a contraceptive method unless they become sexually active. Males who have undergone a vasectomy are not required to use a contraceptive method if at least 16 weeks after the procedure. Same-sex couples are not required to use contraception. 5. Females with a negative pregnancy test at Screening and on Day -1. 6. Willing and able to comply with the protocol. 7. Have not used tobacco products of any kind (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco) for at least 2 weeks prior to the screening visit and are willing to abstain from these products through the end of the study. 8. Non-Japanese subjects only: Subject must be of European, White Latin American, or African descent by subject report. 9. Japanese subjects only: Subject must have been born in Japan. 10. Japanese subjects only: subject must have 2 Japanese biological parents and 4 Japanese grandparents as confirmed by interview. 11. Japanese subjects only: subject has not been living outside of Japan for more than 10 years at the time of the screening visit. 12. Japanese subjects only: subject must not have a significant change in diet since leaving Japan as assessed by the investigator after consultation with the subject. 13. Subject must be healthy in the opinion of the investigator.
Exclusion criteria
Exclusion criteria: 1. Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, chronic gastritis, peptic ulcer disease, etc) that could affect the absorption of study drug 2. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy 3. History of fat malabsorption 4. Dietary restrictions that preclude participation 5. Inability to tolerate oral medication 6. History of allergies or adverse reactions to BH4 or related compounds or to any excipients in the study drug formulation 7. Any clinically significant medical or psychiatric condition or medical history that, in the opinion of the investigator or the medical monitor, would interfere with the subject’s ability to participate in the study or increase the risk of participation for that subject. 8. Alanine aminotransferase or aspartate aminotransferase laboratory values >1.1× the upper limit of normal (ULN) 9. estimated glomerular filtration rate (eGFR) 21 units/week for males or >14 units/week for females 13. A female who is nursing or who is planning to become pregnant 14. QT with Fredericia’s correction (QTcF) =450 msec in males or =470 msec in females (based on the mean of triplicate measurements taken at Screening) 15. Resting heart rate =45 or =100 beats per minute at Screening 16. Resting blood pressure 140/90 mmHg at Screening 17. Subject is, in the opinion of the investigator, unwilling or unable to adhere to the requirements of the study 18. Major surgery within the 90 days prior to Screening 19. Use of an antifolate including, but not limited to, methotrexate, within 1 week prior to Screening and through discharge from the CRU 20. Use of sapropterin dihydrochloride within 1 week prior to Screening and through discharge from the CRU 21. Use of melatonin within 1 week prior to Screening and through discharge from the CRU 22. Positive test for HIV, hepatitis B, hepatitis C 23. Positive screen for drugs with a high potential for abuse or positive screen for alcohol at Screening and/or Check-in 24. Blood loss or donation of =450 ml of blood within 90 days prior to Screening 25. Has used any prescription medication (excluding hormonal contraception and hormone replacement therapy) within 14 days or five half-lives (whichever is longer) prior to Day 1 of the dosing period that the Investigator judges is likely to interfere with the study or pose an additional risk in participating. 26. Has used any over-the-counter medication (including multivitamin, herbal, or homeopathic preparations) during the seven days or five half-lives of th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PK parameters (AUC0-t and Cmax) of BH4 measured using plasma samples at Day 1 and 2 for cohorts 1, 2 , 3, 4, and 5 (non-Japanese). For Cohorts 2 & 5 (Japanese) this occurred on Days 1,2,4 and 5. Plasma was taken at the following timepoints: 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, and 32 hours post dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety outcomes measured using physical examination findings, vital signs assessments, 12-lead ECGs, results of routine clinical laboratory assessments, and AE assessments monitoring of the incidence as well as severity of treatment for emergent AEs (AEs that begin after start of study drug), at study visits and throughout the study.;PK parameters of analytes sepiapterin and BH4, including AUC0-t, Cmax, and Tmax, in the food effect cohort and the relative ratios under fasted and fed conditions, in addition to PK parameters (AUC0-t and Cmax) of sepiapterin in all cohorts, measured using plasma samples at 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, and 32 hours post dose on days 1 and 2 for cohorts 1, 2 (non-Japanese), 3, 4, and 5 (non-Japanese). For Cohorts 2 and 5 (Japanese) this occurred on days 1, 2, 4 and 5 (0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, and 32 hours post dose). | — |
Countries
England, United Kingdom
Contacts
Public ContactMed Info
Outcome results
None listed