A study to evaluate the safety and pharmacokinetics of DB-020 when administered to healthy participants
- Conditions
- OtotoxicityEar - Deafness
- Registration Number
- ACTRN12618001710213
- Lead Sponsor
- Decibel Therapeutics Australia Pty Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 42
1. Ability to communicate with medical team and staff, willingness to participate in the study, willingness to give written informed consent, and willingness to comply with the study restrictions.
2. Healthy men and women aged 18 to 50 years, inclusive, at screening.
3. Weight: greater than or equal to 50.0 kg.
4. Body mass index (BMI): 18.0 to 32.0 kg/m^2, inclusive. BMI = Body weight (kg)/Height^2 (m^2)]
5. The absence of evidence of any clinically significant, in the opinion of the Investigator, active or chronic medical or psychiatric disease or pathology after a detailed medical and surgical history, a complete physical examination including vital signs measurements, 12-lead ECG, and clinical laboratory tests (hematology, serum chemistry, serology, and urinalysis).
6. All values for hematology and for clinical chemistry tests of serum and urine are within the normal range or showing no clinically relevant deviations, as judged by the Investigator, during screening and on the day of admission to the clinical facility.
7. Ability and willingness to abstain from alcohol, caffeine, and xanthine-containing beverages or food (eg, coffee, tea, cola, chocolate, diet pills, energy drinks) from 48 hours (2 days) before check-in until the final follow-up visit.
8. Male subjects, their female partner(s), and female subjects of childbearing potential must agree to use 2 forms of contraception, 1 of which must be a barrier method, during the study and for 90 days after study drug administration. Acceptable barrier forms of contraception are condom and diaphragm. Acceptable forms of contraception for this study for female partner(s) of childbearing potential and premenopausal female subjects are nonhormonal and hormonal intrauterine device (IUD), hormonal birth control pills, hormonal birth control patches, hormonal birth control injections [eg, Depo-Provera(R)], hormonal birth control implants, and NuvaRing(R). Male and female subjects who consider themselves abstinent, and who agree to remain abstinent during the study and for 90 days after study drug administration, will be eligible to participate in the study. Women of nonchildbearing potential are eligible for the study and are defined as 12 months with no menses before screening and a follicle-stimulating hormone (FSH) level greater than 40 IU/L during screening (ie, postmenopausal female subjects), or surgically sterile female subjects, eg, those having undergone total abdominal hysterectomy, bilateral oophorectomy, or bilateral tubal ligation at least 6 months before screening for study participation. Surgically sterile female subjects may participate if they agree to use condoms during the study and for 90 days after study drug administration. Male subjects who have undergone a vasectomy at least 6 months before Screening and who have a documented negative sperm count (eg, medical records or single semen specimen) after the procedure are not required to use contraception.
9. Male subjects must agree to refrain from sperm donation within 90 days after study drug administration.
10. Hearing threshold of 25 dB or better in both ears as assessed with audiometry before randomization.
11. Normal otoscopic examination of both ears (absence of significant scarring of ear canal or tympanic membrane, absence of narrow ear canal preventing injection, etc.).
12. Must be willing to agree to avoid strenuous exercise, sunbathing, and contact sports for the period starting 7 days prior to c
Subjects meeting any of the following exclusion criteria are not to be randomized to study treatment:
1. Female or male subjects with female partners who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 90 days after dosing of study drug.
2. Sustained supine systolic blood pressure greater than 139 or less than 90 mm Hg and supine diastolic blood pressure greater than 89 or less than 50 mm Hg at screening or any day of admission to the clinical facility.
3. Resting heart rate less than 40 beats per minute or greater than 100 beats per minute during screening or on the day of admission to the clinical facility.
4. ECG during screening showing corrected QT interval using Fridericia correction formula (QTcF) greater than or equal to 450 msec. In addition, subjects with any other risk factors for QT/QTcF prolongation or any abnormality in the ECG that, in the opinion of the Investigator, increases the risk of participating in the study will be excluded.
5. Positive results for drugs of abuse, alcohol, or cotinine in the urine at screening or any day of admission to the clinical facility.
6. Positive screening test for hepatitis B surface antigen, hepatitis C antibody, and/or human immunodeficiency virus (HIV) antibodies.
7. Use of any medication (prescription or over-the-counter (OTC), including health supplements and herbal remedies, with the exception of acetaminophen as defined below) within 2 weeks (4 weeks for enzyme inducers including St. John’s Wort [Hypericum perforatum]) or 5 half-lives (whichever is longer) before the first dose of study drug.
8. Routine or chronic use of more than 2 g of acetaminophen daily.
9. Use of any investigational drug or device within 30 days of the first dose of study drug (6 months for biologic therapies) or 5 half-lives of the investigational drug, if known, whichever time period is longer.
10. Exposure to excessively loud noise (eg, concerts, loud noise at the workplace) within 24 to 48 hours before Day 1.
11. History of donation of more than 450 mL of blood within 60 days before dosing in the clinical research center or planned donation before 30 days have elapsed since intake of study drug. This will be verified by the subject’s hemoglobin and hematocrit values. Subjects with clinically significant abnormalities in hemoglobin/hematocrit will be excluded from the study.
12. Plasma, white blood cell, or platelet donation within 7 days of study participation and throughout the study.
13. Lack of venous access or inability to tolerate venipuncture as determined by the Investigator or designee.
14. History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) and/or allergy to the excipients of the study drug.
15. Current smoker, currently using e-cigarettes, or discontinuation of smoking or use of e-cigarettes less than 45 days before the first dose of study drug.
16. History (within 3 months of Screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 g of alcohol).
17. Any major surgery within 4 weeks of study drug administration.
18. History or presence of malignancy within the past 5 years other than past history of localized or surgical removal of focal basal cell skin cancer; cervical cancer in situ treated successfully in the past by local treatment (including but not limited to cryotherapy or laser therapy) or by hysterectomy.
19. Previous participation in the study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary objective is to evaluate the safety and tolerability of one-time administration of intratympanic DB-020 for Injection to healthy volunteer subjects. This will be assessed by looking at the incidence, severity, causality and seriousness of adverse events; monitoring of vital signs; physical examination; otological examination; cardiac telemetry; and any other clinical laboratory parameter abnormalities after a single intratympanic dosing of DB-020. Potential adverse events may include pain, vertigo, self-limiting bleeding, and tympanic membrane perforations, all of which will be assessed by onsite medical monitoring.[Adverse event information will be recorded from the time of informed consent until 29 days after dosing.]
- Secondary Outcome Measures
Name Time Method A secondary objective is to evaluate the plasma PK profile of DB-020 after one-time administration of intratympanic DB-020 for Injection to healthy volunteer subjects. PK parameters determined are to include AUC(0-24), AUC(0-t), AUC(0-inf), C(max), t(max), and T(1/2).[Blood PK samples will be collected for analysis during the treatment period at: 0 (predose), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours, and 7, 14 and 28 days post-dose.<br>];A secondary objective is to evaluate the urine PK profile of DB-020 after one-time administration of intratympanic DB-020 for Injection to healthy volunteer subjects. PK parameters determined are to include AUC(0-24), AUC(0-t), AUC(0-inf), C(max), t(max), and T(1/2).[Urine PK samples will be collected for analysis during the treatment period from: predose, 0-3, 3-6, 6-12, and 12-24 hours postdose.]