None listed
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, parallel-group, single ascending dose study in healthy subjects. LPT99, the study drug is an Apaf1 inhibitor that can permeate the cochlea. LPT99 is being developed as a locally administered otoprotective agent that would specifically block apoptosis in the ear without interfering with anti-tumor activity of the platinum-based chemotherapeutic agent delivered systemically. There are four sequential doses: 25 µg (200 µM), 50 µg (400 µM), 75 µg (600 µM) and 100 µg (797 µM). Approximately 32 healthy male and female subjects with normal baseline hearing will be enrolled, with 8 subjects planned for each dose cohort. Each Subject will receive a dose of LPT99 or matching placebo by transtympanic (TT) administration. In all subjects, study drug will be unilaterally delivered (ie, 1 ear will remain untreated, serving as the control ear for that subject). The study will include sentinel subjects in the initial cohort and all subsequent dose escalation cohorts.
Interventions
The study will be performed at a single investigational site in Australia.
There are Four (4) sequential doses: 25 µg (200 µM), 50 µg (400 µM), 75 µg (600 µM) and 100 µg (797 µM). Approximately 32 healthy male and female subjects with normal baseline
hearing will be enrolled for the study, and each dose cohort will be having 8 subjects.
Only 1 ear will be treated in an individual subject; the other ear will serve as the control ear for that subject. Each cohort will follow a sentinel dosing app
The study will be performed at a single investigational site in Australia. There are Four (4) sequential doses: 25 µg (200 µM), 50 µg (400 µM), 75 µg (600 µM) and 100 µg (797 µM). Approximately 32 healthy male and female subjects with normal baseline hearing will be enrolled for the study, and each dose cohort will be having 8 subjects. Only 1 ear will be treated in an individual subject; the other ear will serve as the control ear for that subject. Each cohort will follow a sentinel dosing approach, in which 1 active and 1 placebo subject will be dosed at least 24 hours prior to the remaining subjects in the cohort. Mode of administration is transtympanic and strategies used to monitor adherence to the intervention is syringe accountability, unblinded pharmacy CRA, direct observation.
Sponsors
Spiral Therapeutics, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female subject, age 18 to 65 years (inclusive) at Screening 2. Provides written informed consent prior to participation in any study procedure 3. Normal hearing, defined as is greater than or equal to 20 dB from 250 Hz to 8 kHz bilaterally 4. Normal tympanogram 5. No known allergies to lidocaine or prilocaine local anesthesia, to EMLA® (lidocaine 2.5% and prilocaine 2.5%) cream, or to phenol 6. Female subjects of childbearing potential, must not be pregnant, lactating, or planning a pregnancy, must have a negative pregnancy test at screening and at Day -1, and must use a medically acceptable method of contraception [e.g., intrauterine device (IUD), intrauterine system (IUS), or hormonal contraception (oral, implant, or injectable) begun >30 days prior to screening]. Acceptable contraceptive options may also include abstinence (if this is the preferred lifestyle for the participant), physical relationship with a same-sex partner or a partner who has had a vasectomy at least 6 months prior to Screening. Subjects must agree to adhere to contraceptive measures from screening through 30 days after study drug administration. 7. Male subjects must be surgically sterile (vasectomy at least 6 months prior to screening) or practice acceptable methods of contraception, and must agree to abstain from sperm donation, from study drug administration through 90 days after administration of study drug. Male subjects must agree to use a condom to protect male and female partners from exposure to study drug. Male subjects with female partners of childbearing potential, must also agree to partner use of hormonal contraception (oral, implant, or injection), an IUD, or an IUS. Complete abstinence from sexual intercourse, if this is the preferred lifestyle for the participant, is an acceptable contraceptive option.
Exclusion criteria
1. Bleeding disorder that could affect the TT study drug administration 2. Use of anticoagulant medication within 30 days prior to screening. 3. History of surgery to the inner ear 4. History of chronic tinnitus or Meniere's disease 5. History of radiation therapy to the head or neck 6. History of chronic middle ear infection, endolymphatic sac surgery 7. History of known hypersensitivity to any components of the study drug or formulation 8. Positive alcohol or urine drug test at Screening or on Study Day -1 9. Positive pregnancy test at Screening or on study Day -1 10. Acute illness or history of illness, that, in the opinion of the Investigator, could pose a threat to or harm the subject, or obscure interpretation of laboratory test results or study data 11. Acute respiratory infection, acute nasopharyngitis, sinusitis, chronic cough, or symptoms of allergic rhinitis 12. Any clinically significant abnormalities on Screening or Day -1 laboratories, as determined by the Investigator 13. Abnormality of tympanic membrane (perforation, retraction, history of any ear surgery, effusion or other middle ear pathology) that would preclude TT administration 14. Received study drug or placebo in another clinical study within the 30 days prior to study drug administration 15. Deemed unsuitable for study participation by the Investigator, based on the Investigator's judgment
Outcome results
None listed