Clinical trial NCT03954600: A Study to Assess the Safety, Tolerability and PK of NPT520-34 in Healthy Subjects
Official title: A Phase 1, Randomized, Double-Blind, Single and Multiple Ascending Dose Trial of the Safety, Tolerability and Pharmacokinetics of NPT520-34 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Phase 1
Safety
Tolerability
Pharmacokinetics
Parkinson's Disease
Amyotrophic Lateral Sclerosis
Lead sponsor: Neuropore Therapies Inc.
Sponsor class: INDUSTRY
Collaborators: name: Celerion
First posted: 2019-05-17
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the PK, safety and tolerability of orally administered NPT520-34 in healthy subjects at single and multiple doses that may be therapeutically relevant.


Eligibility criteria: Inclusion Criteria:

1. informed of, and willing and able to comply with, all of the protocol requirements and the investigational nature of the study, and have signed an informed consent form in accordance with institutional and regulatory guidelines;
2. male or female adults between 18 and 55 years of age, inclusive;
3. female subjects must be of non-childbearing potential (i.e. post-menopausal for at least 2 years) or surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation) or nonsurgically sterile (hysteroscopic sterilization, i.e. Essure);
4. male subjects must be willing to use an adequate barrier method of contraception for the duration of the study and for 90 days after dosing and no sperm donations for the duration of the study and for 90 days after dosing. Male subjects who are surgically sterile (16 weeks post-surgery, or documented proof of Post-Vasectomy Semen Analysis (PVSA) with negative sperm results) need not employ a method of contraception;
5. non-smokers for at least six months;
6. BMI = 18.0 - 32.0 kg/m2 inclusive;
7. in good health, in the judgment of the Investigator, as determined by: 7a. medical history indicative of no serious or severe chronic conditions requiring frequent medical intervention or continual pharmacologic management, and no medical or social conditions that would potentially interfere with the subject's ability to comply with the study visit schedule or the study assessments; 7b. no clinically significant abnormalities in body temperature, heart rate, respiratory rate, blood pressure; 7c. no clinically significant abnormalities in the 12-lead electrocardiogram (ECG); 7d. no clinically significant abnormalities in clinical chemistry (ALT, AST, total bilirubin must be at or below the upper limit of normal and eGFR must be ≥ 90 mL/min), hematology (hemoglobin ≥ 11.5 g/dL for females and ≥ 13 g/dL for males), coagulation and urinalysis; lab tests may be repeated, if necessary (details are provided in the attached flow chart of study assessments).
8. negative results on the following screening laboratory tests: urine drug screen, urine alcohol screen, serum pregnancy test, hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus antibody.

Exclusion Criteria:

1. females of child bearing potential
2. history of a significant medical condition, including cholecystectomy or clinically significant GI tract resection, that may interfere with absorption, distribution or elimination of NPT520-34, or with the clinical and laboratory safety assessments in this study;
3. history of pre-existing thyroid abnormalities, such as hyper or hypothyroidism;
4. history of lactose intolerance;
5. history of drug hypersensitivity and disorders affecting respiratory function (e.g., COPD, asthma) and cardiac disorders predisposing to cardiac adverse events
6. history of or current alcohol abuse and/or other drug addiction \< 2 years prior to screening, or a positive urine drug or alcohol screen (e.g., amphetamines, barbiturates, benzodiazepines, opiates, cannabinoids, alcohol and cocaine);
7. positive for HBVsAg, HCV Ab, HIV Ab;
8. 12 lead ECG showing the following: having a corrected QTc interval \> 450 msec or \<340 msec (Fridericia's correction);
9. sustained supine systolic blood pressure \> 140 or \< 90 mm Hg or supine diastolic blood pressure \> 90 or \< 50 mm Hg at Screening or Day -1. The average of the 2 assessments of BP taken at each visit will be used to exclude a subject;
10. resting pulse rate at screening of \> 100 or \< 45.
11. donated or lost \> 500 mL of blood \< 56 days prior to enrollment into this study;
12. plasma donation within 7 days prior to enrollment into this study;
13. active infection or febrile illness \< 14 days prior to the first dose of study medication;
14. use of prescription (including hormone replacement therapy) or over-the-counter medications or herbal supplements ≤ 14 days prior to dosing and until completion of follow-up visit on Day 7 for the SAD subjects and Day 21 for the MAD subjects;
15. excessive regular caffeine intake (\>250 mg of caffeine per day);
16. have participated in other clinical studies of a new chemical entity within 30 days prior to admission to the CRU.

Primary outcomes:
measure: Safety/Tolerability of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg)
timeFrame: Baseline, Day 1, 2 3, 5 and 7
measure: Maximum observed plasma concentration of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg)
timeFrame: Day 1, 2, 3, 5, 7
measure: Time to maximum plasma concentration of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg)
timeFrame: Day 1, 2, 3, 5, 7
measure: Area under the plasma concentration-time curve from 0 hour to the time of the last quantifiable plasma concentration of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg)
timeFrame: Day 1, 2, 3, 5, 7
measure: Area under the plasma concentration-time curve extrapolated to infinity of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg)
timeFrame: Day 1, 2, 3, 5, 7
measure: Apparent oral clearance of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg)
timeFrame: Day 1, 2, 3, 5, 7
measure: Apparent oral volume of distribution during the terminal phase of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg)
timeFrame: Day 1, 2, 3, 5, 7
measure: Mean residence time of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg)
timeFrame: Day 1, 2, 3, 5, 7
measure: Terminal elimination half-life of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg)
timeFrame: Day 1, 2, 3, 5, 7
measure: Safety/Tolerability as measures of hematology, clinical chemistry, FSH, coagulation and urinalysis of multiple ascending doses (250 mg and 500 mg)
timeFrame: Baseline, Day 2, 4, 7, 11, 12, 13, 14, and 21
measure: Safety/Tolerability as measures of vital signs and physical examination of multiple ascending doses (250 mg and 500 mg)
timeFrame: Baseline, Day 1, 2, 7, 8, 9, 10, 11, 14, 16, 18 Day 21
measure: Safety/Tolerability as measures of continuous telemetry of multiple ascending doses (250 mg and 500 mg)
timeFrame: Baseline, Day 1, 2, 7, 8, 9, 10, 11, 14, and 15
measure: Safety/Tolerability as measures of suicidal ideation, 12-lead ECG, adverse events and serious adverse events of multiple ascending doses (250 mg and 500 mg)
timeFrame: Baseline, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18 Day 21
measure: Safety/Tolerability as measure of continuous ECG of Multiple Ascending Doses (250 mg and 500 mg)
timeFrame: Baseline, Day 1, 7, and 14
measure: Maximum observed plasma concentration (Cmax) after dosing on Day 1 of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Baseline, Day 1 and 2
measure: Maximum observed concentration at steady-state after dosing on Day 14 of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Day 14
measure: Concentration observed at the end of the dosing interval of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Day 14, 16, 18
measure: Time to max. plasma concentration after dosing on Day 1 of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Day 1
measure: Time to reach Cmax,ss of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Day 14, 16, 18 and 21
measure: Area under the plasma concentration-time curve from 0 hour to the time of the last quantifiable plasma concentration of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Baseline, Day 1, 2, 7, 8, 9, 10, 11, 14, 16, 18 and 21
measure: Area under the plasma concentration-time curve extrapolated to infinity after dosing of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Baseline, Day 1, 2, 7, 8, 9, 10, 11, 14, 16, 18 and 21
measure: Area under the concentration time curve from 0-24 hours after dosing on Day 1 of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Day 1
measure: The area under the concentration time curve during a dosing interval (tau) at steady state after dosing on Day 14 of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Baseline, Day 1, 2, 7, 8, 9, 10, 11, 14, 16, 18 and 21
measure: Apparent oral clearance of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Day 1
measure: Apparent total plasma clearance after oral administration, calculated as Dose/AUCtau after dosing on Day 14 of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Day 14
measure: Apparent oral volume of distribution during the terminal phase of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Day 14, 16, 18 and 21
measure: Mean residence time of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Baseline, Day 1, 2, 7, 8, 9, 10, 11, 14, 16, 18 and 21
measure: Terminal elimination half-life of Multiple Ascending Doses (250 mg, 500 mg)
timeFrame: Day 14, 16, 18 and 21
Secondary outcomes:
measure: Maximum Tolerated Dose of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg)
timeFrame: Day 1, 2, 3, 5, Day 7
measure: Maximum Tolerated Dose of Multiple Ascending Doses (250 mg and 500 mg)
timeFrame: Baseline, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18 Day 21
Other outcomes:
measure: Exploratory Biomarkers of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg)
timeFrame: Baseline, Day 1, 2, Day 7
measure: Exploratory Biomarkers of Multiple Ascending Doses (250 mg and 500 mg)
timeFrame: Baseline, Day 1, Day 7, 14, and 21
Locations:
city: Tempe
country: United States
facility: Celerion, Inc
state: Arizona
Study officials:
affiliation: Celerion
name: Danielle Armas, M.D.
role: PRINCIPAL_INVESTIGATOR
References: