Study to Evaluate the Safety and Pharmacokinetics of SPI-1005

Study Overview
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Brief Summary
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A study to determine the safety, tolerability, and pharmacokinetics of SPI-1005 capsules in healthy adults.

Official Title
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A Phase 1, Double-blind, Placebo-controled, Randomized Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of SPI-1005 (Ebselen)in Healthy Adult Subjects

Conditions
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Hearing Loss, Cancer

Intervention / Treatment
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* Drug: SPI-1005
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult male and female subjects Within 15% of their ideal weights (Table of Desirable Weights of Adults, Metropolitan Life Insurance Company, 1983) Medically healthy subjects with clinically insignificant screening results (laboratory profiles, medical histories, ECGs, physical exam); Voluntarily consented to participate in the study; Females of childbearing potential were either sexually inactive (abstinent) for 14 days prior to screening and throughout the study or used one of the following acceptable birth control methods: Intrauterine device (IUD) in place for at least 3 months prior to study; Barrier method (condom or diaphragm) with spermicide for at least 14 days prior to screening through study completion; Stable hormonal contraceptive for at least 3 months prior to study through completion of study; Surgical sterilization (vasectomy) of partner at least 6 months prior to study. Females of non-childbearing potential were surgically sterile (bilateral tubal ligation with surgery at least 6 months prior to study, hysterectomy, or bilateral oophorectomy at least 2 months prior to study). Exclusion Criteria: History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, otologic, or psychiatric disease; History or presence of alcoholism or drug abuse within the past 2 years; Hypersensitivity or idiosyncratic reaction to compounds related to ebselen; Use of any prescription medication within 14 days (with the exception of hormonal contraceptives) prior to or during the study; Use of any over-the-counter medication including vitamins, herbal preparations, antacids, cough and cold remedies, etc., within 7 days prior or during the study; Use of any drugs or substances known to be strong inhibitors or inducers of cytochrome P450 enzymes within 28 days prior to dosing; Abnormal diet (for any reason) during the 30 days prior to dosing; Donation of whole blood within 56 days prior to the study; Plasma donation within 7 days prior to the study; Participation in another clinical trial within 30 days prior to the study; Female subjects who were pregnant or lactating; Hemoglobin < 12.0 g/dL; Orthostatic vital signs which result in: A pulse increase of more than 30 beats per minute after 3 minutes standing (compared with semi-recumbent pulse rate); or A pulse rate greater than 100 bpm after 3 minutes standing; or A drop in systolic blood pressure decrease of at least 20 mm Hg; or A diastolic blood pressure decrease of at least 10 mm Hg within 3 minutes of standing (compared with semi-recumbent blood pressure).

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPI-1005 Capsule 200mg Ebselen x1<br>Lowest Dose Evaluated, 200mg Ebselen Total, Delivered as a Single Dose | Drug: SPI-1005<br>* 200 mg Ebselen oral capsules (SPI-1005), single dose<br>* Other names: 200 mg Ebselen;|
| Experimental: SPI-1005 Capsule 200mg Ebselen x2<br>2x Lowest Dose Evaluated, 400mg Ebselen Total, Delivered as a Single Dose | Drug: SPI-1005<br>* 200 mg Ebselen oral capsules (SPI-1005), single dose<br>* Other names: 200 mg Ebselen;|
| Experimental: SPI-1005 Capsule 200mg Ebselen x4<br>4x Lowest Dose Evaluated, 800mg Ebselen Total, Delivered as a Single Dose | Drug: SPI-1005<br>* 200 mg Ebselen oral capsules (SPI-1005), single dose<br>* Other names: 200 mg Ebselen;|
| Experimental: SPI-1005 Capsule 200mg Ebselen x8<br>8x Lowest Dose Evaluated, 1600mg Ebselen Total, Delivered as a Single Dose | Drug: SPI-1005<br>* 200 mg Ebselen oral capsules (SPI-1005), single dose<br>* Other names: 200 mg Ebselen;|
| Placebo Comparator: SPI-1000 Capsule 0 mg Ebselen Placebo<br>Matching Placebo Capsule, 0mg Ebselen Total, Delivered as a Single Dose | Drug: Placebo<br>* 0 mg Ebselen oral capsules (SPI-1000), single dose<br>* Other names: 0 mg Ebselen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | The primary objective of this study was to evaluate the safety and tolerability of SPI-1005 (ebselen) in healthy subjects. Incidence and severity of Adverse Events were determined in all treatment and placebo groups. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of SPI-1005 and its major metabolites in healthy subjects | Evaluate the single dose pharmacokinetic profile of SPI-1005 in healthy subjects including Tmax, Cmax, of the parent compound and major metabolites. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ebselen