TerminatedPhase 1ACTRN12620000685910

A First-In-Human study to evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of NT-0167 in Healthy Volunteers.

A randomized, double-blind, placebo-controlled single and multiple ascending dose study to test the safety, tolerability, pharmacokinetics and pharmacodynamics of NT-0167 in healthy volunteers

Sponsor

NodThera

Enrollment

80 participants

Start Date

Jun 24, 2020

Study Type

Interventional

Conditions

Inflammation

Summary

This project is testing the safety, tolerability, pharmacokinetics (PK, the amount of study drug in your blood) and pharmacodynamics (PD, how the study drug affects your body) of both single and multiple oral doses of a new drug called NT-0167. Up to eighty (80) healthy men or women of non-child-bearing potential (WNCBP), aged between 18-55 will be enrolled in this study in up to six SAD and up to four MAD cohorts comprising 8 subjects each. This study will enrol approximately 80 participants, in two parts: Part A: will involve a single ascending (increasing) dose (SAD) where approximately 48 participants (6 groups of 8) will be randomised (assigned randomly, like flipping a coin) to receive a single dose of the study drug or placebo. The placebo will look the same as the study drug but will not contain any medicine. Part A (Food Effect): One group from Part A will return for an additional dose to determine the effect of food on the pharmacokinetics (PK) of the study drug. Part B: will involve a multiple ascending (increasing) dose (MAD) where approximately 32 participants (4 groups of 8) will receive one dose of the study drug or placebo daily for 14 consecutive days (14 doses in total). The study is placebo controlled, meaning that some participants will receive capsule(s) containing the active study drug, and some will receive capsule(s) containing placebo. For Part A your total participation will last about 8 weeks, of which you will spend 4 days (3 nights) in the clinic. For Part B your total participation will last about 10 weeks, of which you will spend 17 days (16 nights) in the clinic.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 55 Yearss

Inclusion Criteria9

Signed informed consent and willing and able to comply with the study protocol;
Healthy men or women of non-child bearing potential (WNCBP), 18 to 55 years of age (inclusive) at screening. The health status is verified by absence of evidence of any clinically significant active or uncontrolled chronic disease following a detailed medical history, a complete physical examination including vital signs, laboratory measurements, and 12-lead ECG;
Female subjects must be of non-childbearing potential in accordance with one of the following definitions:
Surgically sterile (by hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy) as documented by a surgical report or by ultrasound, or
Post-menopausal (age-appropriate spontaneous amenorrhoea for equal to or greater than 12 months and follicle-stimulating hormone (FSH) equal to or greater than 40 IU/mL together with the absence of oral contraceptive use for greater than 12 months);
Male volunteers agree to use barrier protection when they engage in sexual relations with women of child-bearing potential (WOCBP) or lactating women for the duration of their participation in the study and until 90 days after EOS.
Body mass index (BMI) between 18 and 32 kg/m2, inclusive, and with a minimum bodyweight of 50 kg;
Has the ability to communicate well with the Investigator and willing to comply with the study restrictions.
Have the intention to be reachable by mobile phone or e-mail during the whole study period.

Exclusion Criteria15

Lactating females;
Female volunteers with a positive pregnancy test at screening or baseline prior to IMP administration;
Evidence (including symptoms, physical signs, and/or laboratory values) of any active or chronic disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator;
Any confirmed or suspected disease or condition associated with immune system impairment, including auto-immune diseases, HIV, asplenia or recurrent severe infections.
Use of chronic (more than 14 days) immunosuppressant or immunomodulatory drugs within the 6 months prior to IMP administration, or isolated (non-chronic) use within 30 days prior to IMP administration;
Any history of severe allergic reaction(s);
Any confirmed drug hypersensitivity reactions (including skin reactions or anaphylaxis), or other known clinically significant allergies;
History of clinically significant systemic disorders including haematological, renal, endocrine, gastrointestinal, hepatic, cardiovascular, pulmonary, dermatological and neurological disorders, or other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers;
Any history of psychiatric condition that may affect participation in the study or preclude compliance with the protocol;
Receipt of any vaccination, other than an influenza vaccine, within 3 months of IMP administration.
Participation in an investigational drug, vaccine or device study within 3 months prior to first dosing or plans to participate in other investigational drug, vaccine or device research during the study period.
Any nutrients known to modulate CYP enzymes activity (e.g., grapefruit or Seville orange containing products or quinine containing drinks (tonic water or bitter lemon)) will not be permitted from 5 days before dosing until the final PK sample is collected;
Donation (or loss) of whole blood of 400 ml or more during the 12 weeks prior to IMP administration;
Donation of plasma or platelets during the 8 weeks prior to IMP administration;
Any other known factor, condition, or disease that, in the opinion of the Investigator, might interfere with treatment compliance, study conduct or interpretation of the results, or may compromise volunteer safety.

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Interventions

Up to eighty (80) healthy men or women of non-child-bearing potential (WNCBP) will be enrolled in this study in up to six SAD and up to four MAD cohorts comprising 8 subjects each. Subjects within each cohort will be randomised to receive either NT-0167 (6 subjects) or placebo (2 subjects). All SAD cohorts and the first MAD cohort will be started with sentinel dosing. Subjects that were enrolled into one of the SAD cohorts will take part in a further, single dose, food effect, cross-over cohort. One of the SAD cohorts will have a second study period in which the same NT-0167 dose will be repeated for evaluation of pharmacokinetics under fed conditions. This will be determined before the subjects of that particular SAD cohort start with the fasted study part. The food cohort will be scheduled to ensure that, for each participant, the fed dose of the IMP is administered at least 14 days after the corresponding fasted dose. NT-0167 will be provided to the subjects in a blinded manner in capsules. Placebo capsules to match NT-0167 will be administered. Placebo will be indistinguishable from active treatment. All doses are for oral administration under direct observation in the Phase 1 unit. The dose shall be administered per below for each cohort: SAD Cohort 1, 10 mg, fasted Cohort 2, 30 mg, fasted Cohort 3, 100 mg, fasted Cohort 4a, 300 mg, fasted Cohort 4b, 300 mg, fed Cohort 5, 1000 mg, fasted Cohort 6, 2000 mg, fasted MAD Cohort 1, 100 mg, fasted, daily for 14 days Cohort 2, 300 mg, fasted, daily for 14 days Cohort 3, 1000 mg, fasted, daily for 14 days Cohort 4, 2000 mg, fasted, daily for 14 days Fasted condition: No food from -8h pre-dose until 4h post-dose; water is permitted, except 1 hour pre-dosing until 1 hour post-dosing. Fed condition: Subjects have to be fasted from 8 hours prior to dose administration except for the standardized high fat meal which will commence 45 minutes prior to dosing and should be consumed within 30 minutes. Fasting then continues until 4 hours post-dose. Water intake is allowed ad libitum during the fasting period, except from 1 hour prior to dosing until 1 hour post-dose. For the MAD cohorts the once or twice daily for 14 days, frequency will be determined by PK parameters in SAD Cohorts, and confirmed by the dose escalation committee.