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A study to determine the safety and tolerability of graded doses of the drug LHF-535 (LHF-535-SDD) in healthy volunteers.

Phase 1
Completed
Conditions
assa Hemorrhagic Fever
Lassa Hemorrhagic Fever
Infection - Other infectious diseases
Registration Number
ACTRN12618001342202
Lead Sponsor
Clinical Network Services (CNS) Pty Ltd
Brief Summary

This study assessed the safety, tolerability, and pharmacokinetics of LHF-535 given as a single oral dose in healthy subjects. Lassa hemorrhagic fever (LHF) is an acute viral illness caused by Lassa virus. The disease is endemic in parts of West Africa (primarily in Sierra Leone, Liberia, Guinea, and Nigeria), where it causes an estimated 300,000 infections and over 5,000 deaths annually. Healthy subjects aged between 18 and 50 years were enrolled. The safety, and pharmacokinetics of LHF-535 were investigated in healthy volunteers in this first in human Phase 1 trial. Oral administration of single increasing doses of LHF-535 were well tolerated at the studied doses. Results from this study support further clinical development of LHF-535. Being a Phase 1 exploratory study, this clinical trial was not formally powered to determine statistically significance.

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
All
Target Recruitment
48
Inclusion Criteria

1.Male or female 18 to 45 years of age, inclusive, at the time of screening.
2.Able to understand the requirements of the study, to provide written informed consent (as evidenced by signature on an informed consent document that is approved by a Human Research Ethics Committee [HREC]), and agreeable to abide by the study restrictions.
3.Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive, at the time of screening and check-in (Day -1).
4.Minimum weight of 50 kg at the time of screening and check-in (Day -1).
5.Good general health (e.g., no chronic health conditions such as hypertension, diabetes, chronic obstructive pulmonary disease, or cardiovascular disease) as determined by the Investigator. Subjects with mild allergies or benign conditions such as Gilbert’s disease may be enrolled at the discretion of the Investigator.
6.Female subjects of child-bearing potential, with a fertile male sexual partner, must use a highly effective method of contraception (oral contraceptive, intrauterine device, or hormonal patch, injectable, or implantable device) in conjunction with a male condom during the screening period and for the entire duration of study participation including the 28-day follow-up. True abstinence from sexual intercourse, in accordance with the preferred and usual lifestyle of the subject, is acceptable. Periodic abstinence or avoiding sexual intercourse on days while the subject is fertile (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), are not acceptable methods of contraception. Non-childbearing potential is defined as postmenopausal as documented by an elevated follicle stimulating hormone (FSH) level or surgical sterility (e.g., tubal ligation, hysterectomy, and/or bilateral salpingo-oophorectomy).
7.Male subjects must either be surgically sterile (vasectomy) or agree to use a male condom as a method of contraception for the entire duration of the study and for 90 days after dosing; the female sexual partner must also use a medically acceptable form of birth control (e.g., oral contraceptive).
8.Male subjects must agree to not donate sperm for the entire duration of the study and for at least 90 days after dosing.

Exclusion Criteria

1.Pregnancy or breastfeeding.
2.A positive screen for drugs of abuse, including alcohol. The screen may be repeated once at the Investigator’s discretion if a false-positive result is suspected.
3.Use of any tobacco- or nicotine-containing products (including but not limited to, cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to check-in (Day -1) or exposure to tobacco or nicotine within 30 days of check-in (Day -1).
4.A positive cotinine test indicating recent nicotine use. The test may be repeated once at the Investigator’s discretion if a false-positive result is suspected.
5.Donated blood within 90 days or plasma within 30 days of dosing on Day 1.
6.Active substance abuse or any medical or psychiatric condition that could jeopardize the subject’s safety.
7.Use of any medications apart from vitamins, acetaminophen, or hormonal contraception within 14 days of dosing on Day 1. Subjects with mild allergies may use antihistamines at the discretion of the Investigator after approval by the Sponsor Medical Monitor.
8.Receipt of an investigational product within 12 weeks prior to dosing on Day 1 (or 5 half-lives, whichever is longer).
9.Any history of cancer; non-melanoma skin cancer or cervical cancer in situ, resected surgically with no evidence of disease, may be enrolled at the discretion of the Investigator.
10.Receipt of an organ transplant (solid or hematopoietic), including corneal transplant.
11.Prolonged QTcF interval >450 ms on electrocardiograms (ECGs) collected during screening, on Day -1, or just prior to dosing on Day 1.
12.Other clinically significant ECG abnormality, as determined by the Investigator.
13.Any clinically significant abnormal hematology, chemistry, or urinalysis value, as determined by the Investigator.
14.Positive test for human immunodeficiency virus (HIV serology) or known HIV infection.
15.Positive result for hepatitis B surface antigen (HBsAg) or for hepatitis C virus (HCV) antibody.
16.Use of alcohol-containing foods or beverages within 72 hours prior to check-in on Day -1 or 72 hours prior to any study visit.
17.Use of caffeine-containing foods or beverages within 24 hours prior to check-in on Day -1 until discharge from the study unit.
18.Febrile illness or significant infection within 48 hours before administration of the first dose of study drug on Day 1.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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