A placebo controlled phase 1 study to determine the safety and tolerability of ascending doses of GT-1 (a new antibiotic) in healthy adult participants following intravenous infusion.
A Phase 1, Randomized, Double-blind, Placebo-controlled, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GT-1 in Healthy Adult Subjects.
Clinical Network Services (CNS) Pty Ltd
64 participants
Mar 14, 2019
Interventional
Conditions
Summary
GT-1, the study drug being researched in this project, is an experimental antibiotic being developed by Geom Therapeutics, Inc. This means that it is not an approved treatment in Australia, and is not yet approved anywhere else in the world. GT-1 is a novel siderophore cephalosporin antibiotic that is intended to treat serious infections. The primary objectives of this study are to assess the safety and pharmacokinetic (PK) characteristics of the GT-1 antibiotic compared to placebo controls when administered by intravenous infusion to healthy adults.
Eligibility
Inclusion Criteria14
- Healthy male or female 18 to 50 years of age, inclusive, at time of consent
- Female subjects of child-bearing potential, if sexually active with a male partner, must agree to and comply with using 1 barrier method (eg, female condom or male partner using a condom) plus 1 other highly effective method of birth control (eg, oral contraceptive, implant, injectable, indwelling intrauterine device, vasectomized partner), or sexual abstinence, for the duration of the study (from signing of consent to FU visit) and for 30 days after last study drug administration. Females of child-bearing potential must also agree not to donate ova or oocytes (ie, human eggs) during the study. To be considered not of childbearing potential, a female must have either a tubal ligation, hysterectomy, bilateral salpingo-oophrectomy, or menopause (last menstruation >12 months and follicle-stimulating hormone in menopausal range).
- Male subjects, if sexually active with a female partner, must agree to and comply with using 1 barrier method of birth control (eg, male condom) plus 1 other highly effective method of birth control in their partner (eg, oral contraceptive; implant, injectable, indwelling intrauterine device), or sexual abstinence, and must not donate sperm, for the duration of the study (from signing of consent to FU visit) and for 90 days after last study drug administration
- Agrees to be available for all study visits and cooperate fully with the requirements of the study protocol, including the schedule of assessments
- Normal clinical examination including:
- a. No physical examination findings that PI determines would interfere with interpretation of study results
- b. Screening visit triplicate ECG without clinically significant abnormalities, including a QTcF interval duration less than or equal to 450 msec obtained as an average from the triplicate screening ECGs after at least 5 minutes in a semi-supine quiet rest position
- c. Hemoglobin/hematocrit, white blood cell count, and platelet count within the normal range of the reference laboratory, unless deemed not clinically significant by the Investigator (eg, asymptomatic Gilbert’s disease)
- d. Serum creatinine, urea, alanine aminotransferase, and aspartate aminotransferase equal to or less than the upper limit of normal for the reference laboratory; results of all other clinical chemistry and urine analytes without any clinically significant abnormality
- e. Estimated creatinine clearance (CrCl) greater than or equal to 80 mL/min as determined by the Cockcroft-Gault formula
- Body mass index greater than or equal to 18.0 and less than or equal to 30.0 kg/m2
- Willing to refrain from over-the-counter (OTC) or prescription medications or nutritional supplements from Screening visit until discharge from the CRU
- Willing to refrain from strenuous physical activity that could cause muscle aches or injury, including contact sports, at any time from Screening visit until completion of the study (FU visit)
- Willing and able to provide written informed consent
Exclusion Criteria20
- Women who are pregnant and/or nursing
- History of any intolerance, hypersensitivity, or allergic reaction to any ß-lactam antibiotic
- History of QT prolongation, clinically significant hypokalemia, or other proarrhythmic conditions
- History of a known or suspected central nervous system disorders, such as hallucinations, suicidal thoughts, suicidal acts, or of a central nervous system disorder that may predispose to seizures or lower the seizure threshold
- History of Clostridium difficile infection
- Hypertension (confirmed systolic BP >140 mm Hg or diastolic BP >90 mm Hg), bradycardia (heart rate <50 bpm), or tachycardia (HR >100 bpm) measured after 10 to 15 minutes of rest at Screening visit
- Surgery within the 3 months before randomization determined by the PI to be clinically relevant
- Experiencing symptoms of acute illness or chronic disease within 30 days before randomization
- History of recent vaccination within 14 days of first dose of study medication
- Positive screen for hepatitis B virus surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) antibody
- Received any prescription or OTC medications, or herbal, nutritional, and dietary supplements within 7 days before randomization, with the exception of hormonal contraception per Inclusion Criterion #2
- Received any systemic antibiotic within 30 days before randomization
- Smoker or nicotine user within the 3 months before randomization
- History of substance abuse or alcohol abuse defined as an average daily intake >3 units, or an average weekly intake >21 units, where 1 unit is equivalent to 1 can or bottle (12 oz) of beer, or 1 measure (1.5 oz) of spirits, or 1 glass (5 oz) of wine within the previous 2 years
- Positive breath test for alcohol or urine screen for drugs of abuse
- Donation of blood or plasma within 30 days before randomization, or loss of whole blood of more than 50 mL within the 30 days before randomization, or receipt of a blood transfusion within 1 year of study enrollment
- Previous participation in this study or previous participation in another study within 30 days (or <5 half-lives of the study drug, whichever is longer) of Day 1; prior participation at any time in non-invasive methodology trials in which no drugs were given is acceptable
- Employee or family member of an employee of the Sponsor, CRU, or clinical research organization at which the study will be conducted
- Unable to cooperate fully with the requirements of the study protocol, including the schedule of assessments, or likely to be non-compliant with any study requirements
- Any disease or condition (medical or surgical) that, by the determination of the PI, might compromise interpretation of safety or PK data, or would place the subject at risk as a result of participation in the study
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Interventions
This study will comprise of 64 healthy adult participants who will receive GT-1 (a new antibiotic) or placebo (saline) by intravenous (IV) infusion. The study is split into two parts: Part 1 and Part 2. Part 1 Part 1 will be split into 5 groups (cohorts) of 8 participants in each group. In each group 2 participants will be sentinel participants meaning they will be dosed and assessed for safety prior to the rest of the group receiving the study treatment. One (1) sentinel participant will be randomised to receive GT-1 and the other sentinel participant will receive placebo. After 24-48 hours, following a positive safety review, the remaining 6 participants will receive the study drug. Of these 6 participants, 5 will receive GT-1 and 1 will receive placebo. Five dose levels of GT-1 will be assessed in Part 1 according to an ascending single-dose regimen (0.5, 1, 2, 3, and 4 g). The starting dose is based on safety results from nonclinical studies. An extra dose cohort may be added in Part 1 if all 5 previous dosages are well tolerated and all accumulated pharmacokinetic (PK) and safety data appear to support the addition of a higher dose. The dose for this cohort is to be determined but will be between 4.5g and 6.0g administered by IV administration. Participants in Part 1 will be admitted to the Clinical Unit for 3 days from 1 day prior to dosing until 2 days after dosing after which they will return to the Clinical Unit on Day 7 for a follow-up visit. Part 2 Part 2 will be split into 3 groups of 8 participants in each group. There are no sentinel participants in the Part 2 groups. In each group participants will be randomised to receive multiple IV infusions of GT-1 or placebo over 7 calendar days. The amount of GT-1 to be infused in each group and the number of infusions will be determined based on the safety information obtained in Part 1. In each group, 6 participants will receive GT-1 infusions and 2 participants will receive placebo infusions. Participants in Part 2 will be admitted to the Clinical Unit for 9 days from 1 day prior to dosing until Day 8 (at least 24 hours after the last dose) after which they will return to the Clinical Unit on Day 12 for a follow-up visit.
Locations(1)
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ACTRN12618001980224