Boceprevir and Ucalm (St John&Apos;s Wort)

NCT01663922 | Completed Phase 1 Results

• 1 other identifier: SSAT 045
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to look at whether taking a new medication for hepatitis C (boceprevir) together with a herbal remedy commonly used for the treatment of depression (SJW) has any effect on the levels of boceprevir in the blood, compared to when boceprevir is taken on its own. Treatment of hepatitis C genotype-1, has recently been significantly improved with the addition of a new class of drugs called protease inhibitors (PIs). Boceprevir belongs to this class of antiviral drugs and it is administered in combinations with other drugs to treat hepatitis C. One of the common side effects of treatment for hepatitis C is low mood (depression) for which treated patients may self-medicate with preparations containing St. Johns Wort (SJW). SJW is known to cause drug interactions, so taking SJW at the same time as boceprevir may result in a change in how both of these drugs usually work. It is therefore important to find out if the levels of boceprevir in the blood are significantly affected by taking SJW. The study aims to help us understand whether it will be safe to take SJW whilst being simultaneously treated for hepatitis C with boceprevir.

Conditions

Hepatitis C

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic of Boceprevir in the Presence of Ucalm (St John's Wort)

  Pharmacokinetic parameters (maximum and trough concentrations, and area under concentratof boceprevir and SJW will be evaluated when given in combination at steady-state to evaluate possible differences in concentrations during co-administration versus drug given alone. The pharmacokinetic parameters calculated for boceprevir and SJW will be Ctrough,the maximum observed plasma concentration (Cmax), time point at Cmax (Tmax), and total drug exposure, expressed as the area under the plasma concentration-time curve. All pharmacokinetic parameters will be calculated using non-compartmental modelling techniques (WinNonlin®) and all statistical calculations performed within-participant changes in the assessed pharmacokinetic parameters (drug alone vs drug combination) will be evaluated by calculating geometric mean ratios.

  6 months

Study Arms (2)

St John's Wort, then Boceprevir

EXPERIMENTAL

D 1-14 St. John's Wort 2 x 300mg (Ucalm(r)) QD D 22-35 St. John's Wort 2 x 300mg (Ucalm(r)) QD D 31-35 Boceprevir 800mg tds D 52-56 Boceprevir 800mg tds

Drug: Boceprevir; Drug: St John's Wort

Boceprevir, then St John's Wort

EXPERIMENTAL

D 10-14 Boceprevir 800mg tds D 22-35 St. John's Wort 2 x 300mg (Ucalm(r)) QD D 31-35 Boceprevir 800mg tds D 43-56 St. John's Wort 2 x 300mg (Ucalm(r)) QD

Drug: Boceprevir; Drug: St John's Wort

Interventions

Boceprevir DRUG

Boceprevir as Victrelis(r) 200mg capsules

Also known as: Boceprevir 800 mg three times daily

Boceprevir, then St John's Wort; St John's Wort, then Boceprevir

St John's Wort DRUG

Each Ucalm(r) tablet contains 300mg of St Johns Wort extract

Also known as: Ucalm (R) tablets, two tablets given once daily

Boceprevir, then St John's Wort; St John's Wort, then Boceprevir

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
• Male or non-pregnant, non-lactating females
• Between 18 to 65 years, inclusive
• Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive.
• Women of childbearing potential (WOCBP), who are sexually active, must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least one month after the study in addition to the consistent and correct use of a condom. Examples of adequate methods of contraception for females in this trial are diaphragm with spermicide, substance and intra-uterine device. Hormonal contraceptives should not be considered a method of contraception and should be avoided if containing drospirenone.
• Willing to consent to their personal details being entered onto The Over volunteering Prevention Scheme (TOPS) database.
• Registered with a GP in the UK
• Willing to bring photo ID to each visit

You may not qualify if:

• Any significant acute or chronic medical illness
• Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
• Positive blood screen for hepatitis B and/or C antibodies
• Positive blood screen for HIV-1 and 2 antibodies
• Current or recent (within three months) gastrointestinal disease
• Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study
• Exposure to any investigational drug or placebo within three months of first dose of study drug (additional check to be made on TOPS www.tops.org.uk).
• Consumption of grapefruit or Seville oranges, or any grapefruit or Seville orange containing product within one week of first dose of study drug and for the duration of the study
• Use of any other drugs, including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs (note OCPs containing drosperinone should be excluded)
• Females of childbearing potential without the use of effective non-hormonal birth control methods, or not willing to continue practising these birth control methods for at least 30 days after the end of the treatment period
• Previous allergy to any of the constituents of the pharmaceuticals administered in this trial

Sponsors & Collaborators

• St Stephens Aids Trust: lead
• University of Liverpool: collaborator
• University of Turin, Italy: collaborator

Study Sites (1)

St Stephen's AIDS Trust

London, SW10 9NH, United Kingdom

Location

Related Publications (1)

• Jackson A, D'Avolio A, Moyle G, Bonora S, Di Perri G, Else L, Simiele M, Singh GJ, Back D, Boffito M. Pharmacokinetics of the co-administration of boceprevir and St John's wort to male and female healthy volunteers. J Antimicrob Chemother. 2014 Jul;69(7):1911-5. doi: 10.1093/jac/dku060. Epub 2014 Mar 6.

  PMID: 24610312 RESULT

MeSH Terms

Conditions

Hepatitis C

Interventions

N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; Hypericum extract LI 160; Tablets

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr Akil Jackson
• Organization: St Stephens AIDS Trust

akil.jackson@chelwest.nhs.uk

0203 315 6503

Study Officials

• Marta Boffito

  HIV Consultant

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2012
• First Posted: August 13, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: September 29, 2014
• Results First Posted: September 29, 2014

Record last verified: 2014-09

Locations

GB (1)