A Phase I Study to Determine the Safety of Multiple Oral Doses of Niclosamide in Healthy Volunteers
An Open-Label, Cross-Over Phase I Study to Determine the Safety, Tolerability and Pharmacokinetics of Multiple Oral Doses of Niclosamide under Fed and Fasted Conditions in Healthy Volunteers
Ala Wai Pharma Pty Ltd
12 participants
Aug 29, 2018
Interventional
Conditions
Summary
A safety study to assess various doses of reformulated niclosamide, under fed and fasted conditions. This study is intended to answer how the reformulation of the drug affects bioavailability and uptake. Niclosamide is an anticestodal drug that has been used to treat tapeworm infection since initial approval in the 1960s. Ala Wai Pharma Pty Ltd is investigating use of niclosamide for treatment of Zika virus infection. This study is a safety and PK study to determine whether daily dosing of approved doses of niclosamide can maintain a plasma concentration of active substance within therapeutic levels.
Eligibility
Inclusion Criteria21
- Adult male and/or female healthy volunteers, age 18–65 years inclusive. Participants are to have evidence of clinically insignificant screening results (e.g. laboratory profiles, medical history, ECGs, physical examinations) as judged by the Investigator.
- Negative urine drug screen /alcohol breath test prior to Day -1.
- Available for the entire study period and willing to adhere to protocol requirements.
- Male participants, and female participants of childbearing potential, must either be sexually inactive (abstinent) for 14 days prior to the first administration of IP and remain so 30 days following the final dosing of the IP, or have been using one of the following acceptable methods of birth control for the times specified:
- Intra-uterine device (IUD) in place for at least 3 months prior to the first administration of IP.
- Double barrier method (e.g., condom and diaphragm).
- Male partner who is surgical sterile (vasectomy) at least 6 months prior to the first administration of IP and is the sole sexual partner for that female participant.
- Adequate hormonal contraception.
- Partners of participants, including same sex couples, should also use effective forms of contraception (e.g. hormonal contraception or IUD).
- Participants who claim to be sexually inactive, but become sexually active during the course of the study must agree to use a double barrier method (e.g., condom and diaphragm) from the time of the start of sexual activity to 30 days following final dose.
- Protocol Number: AWP 2017-01 Ala Wai Pharma Pty Ltd - Confidential
- Version 2.0 Dated 11 July 2018 Page 16 of 66
- In addition, female participants of childbearing potential will be advised to remain sexually inactive or to keep the same birth control method for at least 30 days following the final dosing of the IP.
- Female participants of childbearing potential must not be lactating during the study.
- Females of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first administration of IP:
- Sterilization (with a copy of the confirmation test) and be using a barrier method (condom or diaphragm) throughout the study;
- bilateral tubal ligation with a barrier method (condom or diaphragm) throughout the study;
- hysterectomy;
- bilateral oophorectomy,
- or be postmenopausal with amenorrhea for at least 1 year prior to the first administration of IP and FSH serum levels = 20 IU/L.
- Males must not donate sperm during the study or for 30 days after the final dose of the IP.
Exclusion Criteria9
- History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease, presence or known history of a viral infection (e.g. influenza) within 6 weeks prior to Screening.
- Pregnant women or sexually active women of childbearing age not on contraception as described above.
- Any of the following at Baseline:
- a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3x upper limit of normal (ULN) and bilirubin greater than or equal to 2x ULN, or
- b. ALT greater than or equal to 5x ULN.
- Participation in a clinical trial with an investigational drug within 30 days preceding the trial.
- Donated blood within 45 days preceding the trial
- Participant has known serum hepatitis, is a carrier of the hepatitis B surface antigen (HBsAg) or hepatitis C antibody, or positive for HIV
- In receipt of medications with potential drug-drug interactions with niclosamide, including tizanidine (an absolute contraindication for niclosamide), losetron, levobupivacaine, duloxetine (Cymbalta), duloxetine (Irenka), bendamustine, sodium iodide and ropinirole.
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Interventions
The purpose of the study is to ascertain whether steady state PK of niclosamide at levels therapeutic for Zika virus treatment can be achieved by once daily dosing of niclosamide 2 g. Investigational product, dosage and mode of administration: Niclosamide oral tablet (Yomesan 500 mg chewable tablet, 2 g/day) Duration of treatment: Six days dosing in total, over 20 days (assuming the minimum 2-week washout period): Dosing period 1: 2 g/day for 3 days (Fed/Fasted) Dosing period 2: 2 g/day for 3 days (Fasted/Fed) Dosing periods 1 and 2 will be separated by at least a 14 day washout period. In addition; All dosing is completed in clinic and study unit staff will perform a compliance check of the mouth and hand (if applicable) of each participant following dose administration.
Locations(1)
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ACTRN12618001441202