Study to Investigate the Absolute Bioavailability of Oral Sylibin

Open Label, Randomized, 2 Way-crossover Study to Investigate the Absolute Bioavailability of Oral Sylibin

This clinical trial phase I in healthy volunteers is intended to describe the oral bioavailability of the silybin-phosphatidylcholine complex by calculating the area under the curve (AUC0-? and AUC0-12) after administration of the same dose of oral silybin (AUCo) and intravenous silybin (AUC iv).

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Legalón SIL; Drug: silybin phosphatidylcholine

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy individuals men who give their written consent to participate in the study, after having received information about the design, the project objectives, the risks and that at any moment they can refuse their cooperation.
• Understand the purpose of the study and be available for performing hospital visits and and admissions.
• Age between 18 and 45 years.
• Healthy subjects, without any organic or psychological pathology
• Clinical history and physical examination within normal limits.
• Lack of clinically relevant abnormalities in blood test (hematology, biochemistry, virology) and urine test
• Vital signs and electrocardiographic recording in the normal range.
• Males with childbearing potential partners must agree to use a highly effective method of contraception (such as surgical sterilization, double barrier method) from the moment of signing the informed consent until 6 months after the end of their participation in the study.

Exclusion Criteria:

• Subjects suffering from organic or psychological pathology. Prior to the inclusion of any volunteer it should be considered all security parameters mentioned in the protocol (biochemical markers of kidney damage and / or liver out of the normal range set by the laboratory).
• Subjects who have received prescription drug treatment in the last 15 days or any medication within 48 hours before receiving study medication.
• Subjects with a BMI that is not between 18 and 30.
• Known hypersensitivity to any drug
• Suspected of drug abuse
• Consumers of alcohol daily and / or acute alcohol poisoning in the last week.
• Subjects smoking.
• Have donated blood in the last three months.
• Participation in any other investigational drug study in the previous 3 months
• Not to be able to follow instructions or collaborate during the course of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Legalón Sil i.v 350 mg; 8 healthy volunteers received 1 vial of 350 mg iv of sylibin lyophilisate for solution for infusion (legalon sil) in two hours (single dose).	Drug: Legalón SIL
Experimental: Silybin-phosphatidylcholine oral 360 mg; 8 healthy volunteers received 9 capsules of 40 mg of sylibin each one (360 mg in total) orally.	Drug: silybin phosphatidylcholine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sylibin pharmacokinetic parameters: Maximum plasma concentration (Cmax) obtained in the different treatment groups.	Patient will be hospitalized in the clinical trial unit in order to obtain plasma concentrations previous to the administration of the corresponding dose and at the following times post-administration: : 20min, 40min, 1h, 1h20min, 1h40min 2h, 2h30min, 3h, 4h, 6h, 8h and 12h. Two more plasma concentrations will be obtained at 5 min and 10 mins post- administration of the iv dose. These measures will be calculated in order to describe the bioavailability of oral sylibinobtained in the different treatment groups.	1 Month
Sylibin pharmacokinetic parameters: Area under the curve (AUC) obtained in the different treatment groups.	Patient will be hospitalized in the clinical trial unit in order to obtain plasma concentrations previous to the administration of the corresponding dose and at the following times post-administration: : 20min, 40min, 1h, 1h20min, 1h40min 2h, 2h30min, 3h, 4h, 6h, 8h and 12h. Two more plasma concentrations will be obtained at 5 min and 10 mins post- administration of the iv dose. These measures will be calculated in order to describe the bioavailability of oral sylibinobtained in the different treatment groups.	1 Month

Secondary Outcome Measures

Outcome Measure	Time Frame
Sylibin pharmacokinetic parameters:Tmax, obtained in the different treatment groups.	1 Month
Sylibin pharmacokinetic parameters:t1/2, obtained in the different treatment groups.	1 Month
To estimate the inter and intraindividual coefficient of variation (CV)	1 Month
To evaluate the safety (adverse events, laboratory abnormalities) and tolerability	2 Months

Collaborators and Investigators

• Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• Collaborators: Fundación Mutua Madrileña
• Investigators: Principal Investigator: Mónica Aguilar, MD, Hospital Universitario Ramón y Cajal

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: December 10, 2015
• First Submitted That Met QC Criteria: December 14, 2015
• First Posted (Estimate): December 17, 2015

Study Record Updates

• Last Update Posted (Estimate): July 11, 2016
• Last Update Submitted That Met QC Criteria: July 8, 2016
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Healthy volunteers; Bioavailability; Phase I; Clinical trial; Clinical Pharmacology; Silybin; Liver Trasplantation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Silymarin; Silybin
• Other Study ID Numbers: PK-SIL-FARMA03