A Phase 1 Exploratory Placebo and Active-Controlled, Double-Blind, Single and Multiple-Dose Escalation, Pharmacokinetic, Pharmacodynamic and Food Effect Study of CNSA-001 in Healthy Volunteers

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12617001561370

Acronym

NIL

Enrollment

Registered

2017-11-16

Start date

2017-11-10

Completion date

2018-06-11

Last updated

2018-09-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

The purpose of this study is to establish the safety and tolerability of orally administered CNSA-001 in healthy subjects follow single and multiple-dose escalation This Phase 1 study will support dose selection for future studies in patients with Segawa Syndrome

Interventions

Part A: Subjects in Part A Cohorts 1 through 3 will be randomized to receive single ascending oral doses of CNSA-001, Sapropterin ((6R)-BH4,) or placebo. Cohort 1 will receive a si ngle 2.5 mg/kg oral dose of CNSA-001 or (6R)-BH4 or Placebo Cohort 2 will receive a single 7.5 mg/kg oral dose of CNSA-001 or (6R)-BH4 or Placebo Cohort 3 will receive a single 20 mg/kg) oral dose of CNSA-001 or (6R)-BH4 or Placebo Subjects in Part A Cohorts 4 and 5 will be randomized to receive single ascending oral doses of CNSA-001 or placebo. Cohort 4 will receive a single oral dose of CNSA-001 (60 mg/kg) or Placebo Cohort will receive a single oral dose of CNSA-001 (90 mg/kg) or Placebo Subjects in Part A Cohort 6 will receive 2 oral doses of CNSA-001 (10 mg /kg) separated by 1 week in a fasted and fed state. Subjects in Cohort 6 of Part A will be fed a standard high-fat (approximately 50 percent of total caloric content of the meal) and high-calorie (approximately 800 to 1000 calories) meal starting 30 minutes prior to receiving their second oral dose of CNSA-001 on Day 8. Part B: Subjects in Part B Cohorts 1 through 3 will be randomized to receive multiple oral doses of either CNSA-001 or placebo daily for 7 days at a low, medium, or high oral dose level. Cohort 1 will receive a multiple oral doses of CNSA-001 (5 mg/kg) or Placebo Cohort 2 will receive a multiple oral doses of CNSA-001 (20 mg/kg) or Placebo Cohort 3 will receive a multiple oral doses of CNSA-001 (60 mg/kg) or Placebo

Study design

Allocation

Randomised controlled trial

Intervention model

Parallel

Primary purpose

Treatment

Masking

Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

1. Males or females 18 years old and above and weighing equal to or greater than 55 kg and less than or equal 100 kg 2. Informed consent 3. Females must be either postmenopausal for at least 1 year or surgically sterile (having undergone tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 6 months or, if of childbearing potential and not abstinent, willing to use an effective method of contraception from Screening through 30 days after the last dose of study drug: -Hormonal contraception (stable dose for 3 months) -Intrauterine device/Intrauterine Hormone-releasing System -Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, condom) Females who are abstinent will not be required to use a contraceptive method unless they become sexually active. 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 30 days after the last dose of study drug. Males must also refrain from sperm donations during this time period. 5. Males who are abstinent will not be required to use a contraceptive method unless they become sexually active. 6. Females with a negative pregnancy test at Screening and on Day 1 prior to dosing 7. Creatinine clearance (CrCl) >90 mL/min 8. Willing and able to comply with the protocol 9. Have not used tobacco (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco) for 2 weeks prior to the Screening visit and willingness to abstain from these products through the completion of the study

Exclusion criteria

1. Any significant chronic medical illness, as determined by the Investigator 2. Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, chronic gastritis, peptic ulcer disease, etc.) that could affect the absorption of the study drug CNSA-001 3. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy 4. Inability to tolerate oral medication 5. History of allergies or adverse reactions to BH4 or related compounds or to any excipients in the study drug formulation 6. 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 7. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) laboratory values greater than 2 times the upper limit of normal (ULN) 8. Gilbert’s Syndrome 9. 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. 10. Current participation in any other investigational drug study or participation within 30 days prior to Screening 11. History of alcohol or drug abuse within last 6 months prior to screening, current evidence of substance dependence or self-reported alcoholic intake >2 drinks/day 12. A female who is nursing or who is planning to become pregnant 13. QTcF (QT with Fredericia’s correction) equal to 460 msec in males and equal to 480 msec in females (based on the mean of triplicate measurements taken at Screening) 14. Resting heart rate of equal to or less than 40 or equal to or greater than 110 beats per minute (bpm) or resting blood pressure less than 90/40 mmHg or greater than 150/90 mmHg at Screening or prior to the first administration of study drug 15. Any other abnormal vital signs that are considered to be clinically significant by the Investigator 16. Is, in the opinion of the Investigator, unwilling or unable to adhere to the requirements of the study 17. Major surgery within the prior 90 days 18. Currently taking an antifolate including, but not limited to, methotrexate 19. Positive test for HIV, hepatitis B, or hepatitis C

Outcome results