Study To Determine The Effects Of Doses Of Relacatib On The Metabolism Of Acetaminophen, Ibuprofen And Atorvastatin

A Study to Evaluate the Potential for Pharmacokinetic Interaction Between SB 462795 and SSRIs in Healthy Subjects [3A]

Relacatib is being developed for the treatment of osteoporosis, osteoarthritis and possibly other bone disorders. Recent results suggest that relacatib interacts with the way our bodies metabolise drugs and so some drugs which are commonly prescribed to the intended target patient population could be affected by giving relacatib at the same time. The purpose of this study is to evaluate the effect of repeat dose administration of relacatib on the way subjects bodies metabolise three commonly prescribed medications in the osteoarthritis population: ibuprofen, acetaminophen, and atorvastatin.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: Acetaminophen; Drug: Ibuprofen; Drug: Atorvastatin; Drug: Relacatib

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

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • GSK Investigational Site
  • Liège, Belgium, 4000
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy
• Postmenopausal
• Body weight > 50 kg
• Body mass index (BMI) between 19 and 30
• The subject is willing and able to give a signed and dated written informed consent prior to admission to the study
• The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

Exclusion Criteria:

• Subjects with known morphea or sclerodermia
• Subjects with a history of myocardial infarction.
• Subjects with a history of renal/or hepatic disease unless the disease has been successfully treated and is no longer active; subjects with any evidence of renal/ or hepatic impairment on the screening physical and laboratory examination.
• Subjects with history of hypertension or systolic blood pressure
• Subjects with history of diabetes
• History of regular alcohol consumption exceeding 7 drinks/week (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months of screening.
• History of use of tobacco- or nicotine-containing products within 6 months of screening, or a positive urine cotinine indicative of smoking at screening.
• Positive urine drug screen including alcohol (or alcohol breath test) at screening.
• Positive for HIV, hepatitis B virus or hepatitis C virus.
• Donation of blood in excess of 500 mL within 56 days prior to dosing
• History of sensitivity or contraindications to any of the study medications (i.e., relacatib, paracetamol, ibuprofen or atorvastatin) or components thereof.
• Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
• Subjects whom are judged by the investigator to be at risk for acute angle closure glaucoma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Session 1; Subjects will receive 500 mg acetaminophen on Day 1, 400 mg ibuprofen on Day 2, 40 mg atorvastatin on Day 3.	Drug: Acetaminophen; Acetaminophen will be administered orally; Drug: Ibuprofen; Ibuprofen will be administered orally; Drug: Atorvastatin; Atorvastatin will be administered orally
EXPERIMENTAL: Session 2; Subjects will be randomized to receive relacatib 60 mg or 120 mg from Day 1-14. On Day 15 subjects will receive 500 mg acetaminophen, 400 mg ibuprofen on Day 16 and 40 mg atorvastatin on Day 17 with usual dose of relacatib.	Drug: Acetaminophen; Acetaminophen will be administered orally; Drug: Ibuprofen; Ibuprofen will be administered orally; Drug: Atorvastatin; Atorvastatin will be administered orally; Drug: Relacatib; Subjects will administer 60 or 120 mg tablets in Session 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary objective of this study is to characterize the effect of relacatib at steady-state on the pharmacokinetics of a single oral dose of acetaminophen, ibuprofen and atorvastatin in healthy postmenopausal females.	Up to Day 17

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the safety and tolerability of the concomitant administration of oral doses of relacatib and acetaminophen, ibuprofen and atorvastatin. To describe the changes from baseline in serum CTXI levels for each relacatib dose tested.	Up to Day 17

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 19, 2006
• Primary Completion (ACTUAL): December 15, 2006
• Study Completion (ACTUAL): December 15, 2006

Study Registration Dates

• First Submitted: December 11, 2006
• First Submitted That Met QC Criteria: December 11, 2006
• First Posted (ESTIMATE): December 13, 2006

Study Record Updates

• Last Update Posted (ACTUAL): October 4, 2017
• Last Update Submitted That Met QC Criteria: October 2, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Osteoarthritis; Osteoporosis; Postmenopausal
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; 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; Antipyretics; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Acetaminophen; Ibuprofen
• Other Study ID Numbers: SB-462795/008