Pharmacokinetic Study to Investigate the Bioavailability and Tolerability of 3 Oral Formulations of Sodium Thiosulfate

Study Overview
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Brief Summary
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Chronic treatment and prophylaxis of vessel and soft tissue calcification as well as of renal calculi could be a future indication for sodium thiosulfate (STS). Using an oral formulation might increase the compliance and treatment success compared to parenteral administration. Three gastro-resistant formulations of STS for oral administration were developed with different release characteristics: fast-release, medium-release and slow-release tablets. Aim of the enteric coating was to increase the oral bioavailability of STS. The bioavailability and tolerability of these formulations for oral administration in healthy volunteers will be compared in this clinical trial.

Official Title
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Phase I Pharmacokinetic Pilot Study to Investigate the Bioavailability and Tolerability of Three Different Oral Formulations of Sodium Thiosulfate

Conditions
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Healthy

Intervention / Treatment
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* Drug: Sodium thiosulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female healthy subjects ≥ 18 years Negative pregnancy test in female subjects of childbearing age Able to understand character and individual consequences of the clinical trial and to provide written informed consent to participate in the study Exclusion Criteria: Pregnant or lactating subjects. Renal impairment (creatinine clearance <60ml/min) Concomitant medication Gastrointestinal diseases History of alcohol abuse, illicit drug use, significant mental illness, physical dependance to opioid, other drug abuse or addiction (last 12 months)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Other
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fast first<br>Sodium thiosulfate fast release formulation first, followed by medium and slow | Drug: Sodium thiosulfate<br>* oral administration of thiosulfate<br>|
| Experimental: Medium first<br>Sodium thiosulfate medium release formulation first, followed by slow and fast | Drug: Sodium thiosulfate<br>* oral administration of thiosulfate<br>|
| Experimental: Slow first<br>Sodium thiosulfate slow release formulation first, followed by fast and medium | Drug: Sodium thiosulfate<br>* oral administration of thiosulfate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative bioavailability of STS after oral administration based on urinary excretion of TS and sulfate |  | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events |  | 7 weeks | 
| TS excretion in urine | amount excreted within 48h and fraction (amount/dose) of administered thiosulfate | 48 hours | 
| TS excretion in urine: amount | amount excreted within 48h | 48 hours | 
| TS excretion in urine: fraction of administered TS | excreted / administered | 48 hours | 
| Sulfate excretion in urine: amount | amount excreted within 48h | 48 hours | 
| Sulfate excretion in urine: fraction of administered TS | excreted / administered | 48 hours | 

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