A healthy volunteer study evaluating the the safety, tolerability, and pharmacokinetics of RT234
A Phase I, Two-Part, Single-Center, Open-Label, Randomized, Cross Over, Single Ascending Doses (SAD), followed by a Multiple Ascending Doses (MAD) Safety and Pharmacokinetic Study of RT234 in Healthy Subjects
Clinical Network Services Pty Ltd
32 participants
Jul 30, 2018
Interventional
Conditions
Summary
This is a healthy volunteer study to evaluate the safety, tolerability, and pharmacokinetics of a new drug called RT234.
Eligibility
Inclusion Criteria10
- Healthy male or female, 18 to 45 years of age (inclusive at time of informed consent)
- Willing and able to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures
- Normal heart, lung, kidney, and liver function based on physical examination
- Systolic blood pressure of 100-145 mmHg, diastolic blood pressure of 50-90 mmHg, and a resting heart rate of 40-100 beats per minute at Screening
- Body mass index within the range of 18.0 to 32.0 inclusive at Screening
- Must be a non-smoker or ex-smoker with less than a 5-pack year history of smoking (including the use of electronic cigarettes) and have ceased smoking over 1 year prior to Screening; or a social smoker (defined as less than 10 cigarettes in the previous 12 months)
- Females must be non-pregnant and non-lactating, and either surgically sterile or use highly effective contraceptive method from Screening until study completion, including the follow-up period, or be post menopausal for more than 12 months. Postmenopausal status will be confirmed through testing of follicle stimulating hormone (FSH) levels . Females who are abstinent from heterosexual intercourse will also be eligible.
- Males must be surgically sterile (more than 30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a woman of child-bearing potential, the participant and his partner must be surgically sterile or using an acceptable, highly effective contraceptive method from Screening until study completion, including the follow-up period.
- Subjects with same sex partners (abstinence from penile-vaginal intercourse) are eligible when this is their preferred and usual lifestyle.
- Women of child-bearing potential must have a negative pregnancy test at Screening and Day 1 and be willing to have additional pregnancy tests as required throughout the study
Exclusion Criteria20
- Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the follow-up period
- Known hypersensitivity to active drug substance or drugs of the same class, or any excipients of the drug formulation(s)
- History or clinical evidence of any disease and or medical condition which may interfere with the absorption, distribution, metabolism, or excretion of the study treatment
- Has serum transaminase levels greater than three times the upper level of normal
- Abnormal orthostatic vital signs (at screening) defined as a decrease of greater than or equal to 20 mmHg in systolic blood pressure and or a decrease of greater than or equal to 10 mmHG in gystolic blood pressure and or greater than 25 beats per minute increase in heart rate within 3 minutes of standing, or with symptoms of lightheadedness, dizziness, or fainting upon standing.
- History of hypotension including fainting, syncope, orthostatic hypotension, and or vasovagal reactions
- History of cardiopulmonary diseases (cardiovascular, pulmonary, and pleural disorders) and/or cardiopulmonary symptoms of breathlessness, cough and or wheezing
- History of drug abuse
- History of alcohol abuse (defined as more than 12 standard drinks per week), consumption food or drink containing grapefruit or seville orange within 72 hours before start of dosing or expected to do so through end of study/early termination
- Use of any prescription drugs (other than hormonal contraception; OCP’s, long-acting implantable hormones, injectable hormones, a vaginal ring or an IUD), non-prescription drugs, herbal remedies, supplements or vitamins 2 weeks prior to dosing and during course of study without prior approval of the Investigator and Medical Monitor.
- History of retinitis pigmentosa
- Vision loss due to non-arteritic anterior ischemic optic neuropathy or other optic perfusion impairment
- History of priapism or anatomical deformation of the penis
- History of sudden sensorineural hearing loss (SSHL), need for hearing aids, and or other documented hearing loss
- A corrected QT interval using Fridericia’s formula (QTcF) greater than 450 msec
- Has evidence of significant obstructive lung disease on spirometry. Subjects with any of the following criteria will be excluded:
- a. Forced expiratory volume in 1 second (FEV1 ) less than 60% (predicted) (pre bronchodilators); or
- b. Forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC) less than 65% (pre-bronchodilators)
- Use of any IP or investigational medical device within 30 days prior to Screening, or 5 half-lives of the product (whichever is the longest) or participation in more than four investigational drug studies within 1 year prior to Screening
- Presence or history of any condition that, in the view of the Investigator, may affect full participation or compliance with the protocol, or would affect safety
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Interventions
RT234 consists of capsules of a dry powder formulation containing either 0.2 milligram or 0.6 milligram of active substance. Each dose of RT234 is administered via oral inhalation with a non invasive, dry powder inhaler. This is a Phase 1, two-part, open-label, randomized, cross-over safety and PK study of RT234 in healthy subjects. Part 1 is the Single Ascending Dose (SAD) portion. Part 2 is the Multi-Ascending Dose (MAD) portion. For Part 1 (SAD) of the study, there are 4 cohorts with 6 participants in each cohort. Participants in each cohort will receive a single dose RT234. Cohort 1 participants will receive a single dose of 200 mcg of RT234. Cohort 2 participants will receive a single dose of 600 mcg of RT234 and a single dose of 20 mg of the oral comparator, vardenafil. Cohort 3 participants will receive a single dose of 1200 mcg of RT234. Cohort 4 participants will receive a single dose of 2400 mcg of RT234. In Cohort 2 only, one half of of the participants will be randomized to receive a single inhaled dose of RT234 (600 mcg) on Day 1 while the other half will receive a single 20mg oral dose of the comparator. Participants will then cross-over to receive their alternate treatment (RT234 or oral comparator) on Day 3 For Part 2 (MAD) of the study, 8 participants will receive 2 doses of RT234 on the first day, 3 doses of RT234 on the second day, and 4 doses of RT234 for the next 6 consecutive days (one dose of RT234, four times a day, from Day 3 - Day 9) The dose for Part 2 (MAD) will be the highest safe dose as determined in Part 1 (SAD) by the Safety Monitoring Committee. Depending on the results of Part 1 (SAD), participants participating in Part 2 (MAD) could receive up to a total of 9600 mcg/day of RT234 (2400 mcg four times a day) Each dose administration will be observed by the study site staff to ensure correct technique is being utilised and that the entire dose has been inhaled. The study site staff will also evaluate the used capsule after administration to confirm that no dose remains in the used capsule. Participation ranges from 7 days to 14 days, depending on which part of the study and which cohort the participant is assigned to. Participants will only be enrolled in 1 part. Participants in Part 1 cannot participate in Part 2.
Locations(1)
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ACTRN12618001077257