A Study of Safety and Tolerability of NOX66 in Healthy Volunteers

NCT03780465 | Withdrawn Phase 1 DMC

• 1 other identifier: NOX66-003
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1, double- blinded, randomised, placebo-controlled study to assess safety, tolerability and pharmacokinetics of 2 formulations of NOX66 in healthy subjects when administered over 4 cohorts as single NOX66 dose of 400 mg and 600 mg in comparison to single oral dose of 400 mg idronoxil.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (5)

• Area Under the concentration-time Curve for idronoxil from NOX66 and oral formulations

  AUC will be determined form blood plasma and urine taken at pre-dose and post dose time points.. Plasma concentration data for idronoxil will be summarised for the PK population by treatment and scheduled sampling time.

  Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

• Maximal observed concentration for idronoxil levels from NOX66 and oral formulations

  Maximal observed concentration of idronoxil will be assessed from blood plasma taken at pre-dose and post dose time points .

  Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

• Time to reach maximum observed concentration from idronoxil for NOX66 formulations and oral

  Time to occurrence of maximum observed concentration will be measured from blood plasma taken at pre-dose and post dose time points.

  Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

• Terminal half-life of Plasma and Urine idronoxil from NOX66 and oral formulations and oral

  Apparent terminal half-life will be assessed from blood plasma and urine taken at pre-dose and post dose time points.

  Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose.

• Total body clearance of idronoxil after administration of NOX66 and oral formulations

  Total body clearance will be assessed from blood plasma and urine taken at pre-dose and post dose time points.

  Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose

Secondary Outcomes (5)

• Number of subjects with treatment-related adverse events

  From screening up to end of study (144 hours)

• Relative bioavailability of NOX66 formulations compared to the oral idronoxil

  From pre-dose up to end of study (144 hours)

• Number subjects with clinical significant ECGs

  Telemetry 10 hours prior dosing continuously for 24 hours post dosing (cohorts 1, 4 and 5); safety ECGs for all cohorts pre dose and post dose to 144 hrs or end of study.

• Number subjects with clinical significant abnormalities in lab tests

  Screening to 7 days

• Number subjects with clinical significant abnormalities in vital signs

  Screening to 7 days

Study Arms (3)

Oral idronoxil

ACTIVE COMPARATOR

10 male and female subjects randomised to 400 mg active Oral idronoxil suspension or oral placebo suspension (n=8 active; n= 2 placebo).

Drug: Oral idronoxil suspension

NOX66 400 mg

EXPERIMENTAL

10 male and female subjects randomised to 400 mg active NOX66 (A) suppository or 400 mg active NOX66 (B) suppository or suppository placebo (n=8 active; n= 2 placebo).

Drug: NOX66 (A); Drug: NOX66 (B)

NOX66 600 mg

EXPERIMENTAL

10 male and female subjects randomised to 600 mg active NOX66 (A) suppository or 600 mg active NOX66 (B) suppository or suppository placebo (n=8 active; n= 2 placebo).

Drug: NOX66 (A); Drug: NOX66 (B)

Interventions

Oral idronoxil suspension DRUG

Idronoxil powder up to 150 ml ORA-BLEND® flavoured syrup

Oral idronoxil

NOX66 (A) DRUG

Idronoxil formulated in suppository base A

NOX66 400 mg; NOX66 600 mg

NOX66 (B) DRUG

Idronoxil formulated in suppository base B

NOX66 400 mg; NOX66 600 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of informed consent.
• Male and/or female subjects, 18 - 55 years of age.
• BMI of 17.5 to 30 kg/m2 and a total body weight \>50 kg.
• Negative hepatitis panel (including HBsAg and anti-HCV) and negative HIV antibody screens.
• Negative test for selected drugs of abuse.
• Males and females of childbearing potential who are not abstinent from heterosexual intercourse as part of their usual and preferred lifestyle must agree for the study duration and for 3 months after study to use two effective means of contraception (hormonal contraception, intrauterine device, condoms). Surgical sterilisation \>3 months prior to Screening is acceptable.
• Postmenopausal females should have menopause confirmed by follicle-stimulating hormone (FSH) testing.
• Subjects who have same sex partners or who practice abstinence in line with standard and preferred lifestyle will not be required to use contraception.

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated asymptomatic, penicillin, seasonal allergies at the time of dosing).
• lead ECG at screening or at first admission to the study center. Subjects with a QTcF interval \>450 msec or QRS interval ≥110 msec will be excluded.
• Treatment with an investigational drug /device within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study medication (whichever is longer).
• Other severe acute or chronic medical or psychiatric conditions or a laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgement of the principal investigator (PI), would make the subject inappropriate for entry into this study.
• Abnormal nutritional status, including unconventional and abnormal dietary habits; excessive or unusual vitamin intake; malabsorption (oral cohort only).
• Has history of significant drug or alcohol abuse within past 5 years or has a positive drug screen.
• Smoking or use of nicotine-containing substances within past 2 months with the exception for social smokers who will be allowed a maximum of 5 cigarettes per week.
• Has use of any prescription or nonprescription medications or herbal supplements, except for paracetamol, within 14 days before the first dose of study drug, unless approved by the PI and sponsor.
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy, cholecystectomy, and hernia repair will be allowed.
• Consumption of grapefruit/starfruit-containing foods and beverages or other CYP3A4 inhibitors or inducers for 72 hours prior to Screening and during the entire study.
• Donation of blood from 30 days prior to Screening through Study Completion/End of treatment (ET), inclusive, or plasma from 2 weeks prior to Screening through Study Completion/ET, inclusive.
• Any acute or chronic condition that, in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in this clinical study.
• Use of alcohol within previous 24 hours or use of caffeine within previous 12 hours of Day -1 admission.

Sponsors & Collaborators

• Noxopharm Limited: lead

Study Sites (1)

Nucleus Network Ltd

Melbourne, Victoria, 3004, Australia

Location

Study Officials

• Marinella Messina, PhD

  Noxopharm Limited

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The pharmacist preparing the study medication and the study nurse administering the study medication are not masked.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 19, 2018
• Study Start: March 1, 2019
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: May 28, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 12 months after study completion

Locations

AU (1)