Study to Evaluate the Safety and Pharmacokinetics of SPI-1005

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

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

Study Overview

• Status: Completed
• Conditions: Cancer; Hearing Loss
• Intervention / Treatment: Drug: SPI-1005; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • MDS Pharma Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sound Pharmaceuticals, Incorporated
• Investigators: Principal Investigator: James C. Kisicki, M.D., MDS Pharma Services

Publications and helpful links

General Publications

• Garland M, Hryckowian AJ, Tholen M, Bender KO, Van Treuren WW, Loscher S, Sonnenburg JL, Bogyo M. The Clinical Drug Ebselen Attenuates Inflammation and Promotes Microbiome Recovery in Mice after Antibiotic Treatment for CDI. Cell Rep Med. 2020 Apr 21;1(1):100005. doi: 10.1016/j.xcrm.2020.100005.
• Lynch E, Kil J. Development of Ebselen, a Glutathione Peroxidase Mimic, for the Prevention and Treatment of Noise-Induced Hearing Loss. Semin Hear 2009; 30(1): 047-055

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): August 1, 2006
• Study Completion (Actual): August 1, 2006

Study Registration Dates

• First Submitted: October 10, 2011
• First Submitted That Met QC Criteria: October 14, 2011
• First Posted (Estimate): October 17, 2011

Study Record Updates

• Last Update Posted (Estimate): June 29, 2016
• Last Update Submitted That Met QC Criteria: June 27, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Ebselen
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gastrointestinal Agents; Neuroprotective Agents; Protective Agents; Anti-Ulcer Agents; Antioxidants; Ebselen
• Other Study ID Numbers: SPI-1005-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided