A Phase 1, Randomized, Open-Label, Crossover Study to Evaluate the Relative Oral Bioavailability of 2 Formulations of PTC923 and the Food Effect on the Phase 3 Formulation When Administered as a Single Dose to Healthy Subjects

Phase 1

Completed

• Conditions: Phenylketonuria (PKU); Metabolic and Endocrine - Metabolic disorders

• Registration Number: ACTRN12622000523707
• Lead Sponsor: PTC Therapeutics Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-04-01
• Study Completion: 2022-07-12
• Last Update Posted: 24 October 2022

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

Individuals eligible to participate in this study include those who meet all of the following
inclusion criteria:
1. Males or females aged between 18 and 55 years old and have a Body Mass Index between 18.5 and 30.0 kg/m squared
2. Subjects 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 must have a negative pregnancy testing at Screening and agree to abstinence or the use of effective forms of contraception (with a failure rate of less than 1% per year when used consistently and correctly. Highly effective contraception or abstinence must be continued for the duration of the study and for up to 30 days after the last dose of study drug.
4. Males with female partners of childbearing potential must agree to use barrier contraceptive 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 (eg, 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 end of study.
8. Part A only: Subject must be willing and able to consume the entire low-fat breakfast in the designated timeframe.
9. Part B only: Subject must be willing and able to consume the entire high-fat breakfast in the designated timeframe.

Exclusion Criteria

Individuals are not eligible to participate in this study if they have met or meet any of the
following 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 greater than 1.5× the
upper limit of normal (ULN)
9. Serum creatinine greater than or equal to 1.5× ULN at Screening
10. Any other clinically significant laboratory abnormality at the Screening Visit or prior to the administration of the first dose of study drug. In general, each laboratory value from screening and baseline chemistry and hematology panels should fall within the limits of the normal laboratory reference range, unless deemed not clinically significant by the investigator. The investigator may repeat laboratory testing one time in the event of an out-of-range laboratory value to confirm eligibility.
11. Current participation in any other investigational drug study or participation within 30 days prior to Screening
12. History of alcohol or drug abuse within last 6 months prior to Screening, current evidence of substance dependence or self-reported alcoholic intake greater than 10 standard drinks/week
13. A female who is nursing or who is planning to become pregnant
14. QTcF (QT with Fredericia’s correction) greater than or equal to 450 msec in males and greater than or equal to 470 msec in females
(based on the mean of triplicate measurements taken at Screening)
15. Resting heart rate less than or equal to 45 or greater than or equal to 100 beats per minute
16. Resting blood pressure less than 90/50 mmHg or greater than 150/95 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 clinic
20. Use of sapropterin dihydrochloride within 1 week prior to Screening and through discharge from clinic
21. Use of melatonin within 1 week prior to Screening and through discharge from clinic
22. Positive test for human immunodeficiency virus, hepatitis B, or hepatitis C
23. Positive screen for drugs with a high potential for abuse or positive screen for EtOH at
Screening and Check-in
24. Blood donation of greater than or equal to 450 mL of blood within the 90 days prior to Screening

Study & Design

• Study Type: Interventional
• Study Design: Not specified