WithdrawnPhase 1

Study to Determine the Effect of Itraconazole on the Pharmacokinetics of Rilapladib (SB659032) in Healthy Volunteers

A Phase I, Two-part, Open-label Study to Evaluate the Pharmacokinetics of Rilapladib (SB-659032) and Its Metabolites, and to Determine the Effect of Repeat Dose Itraconazole on the Pharmacokinetics of Rilapladib in Healthy Volunteers

Lead sponsor

GlaxoSmithKline

Asset

Rilapladib

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criterion

•Age 18-65

Primary endpoints

•Cmax, time of occurrence of Cmax (Tmax)•AUC from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity))•Cmax, Tmax, AUC(0-tau), and AUC from time zero (pre-dose) to time of last

Identifiers

Registered as

Org study ID201274

NCT IDNCT02130661

Timeline

Milestones

Study first posted2014-05-05estimated

Last update posted2016-12-13estimated

Study start2017-10 (month precision)

Primary completion2018-01estimated (month precision)

Study completion2018-01estimated (month precision)

Assets

Drug assets

Rilapladib

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age18 Years

Maximum age65 Years

SexAll

Healthy volunteersAccepted

Inclusion criteria

•Male or female aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.

•Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and Electrocardiogram (ECG). A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator in consultation with the Glaxosmithkline (GSK) Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.

•A subject with an alanine aminotransferase (ALT), alkaline phosphatase or bilirubin laboratory result outside the reference range may be included only if the Investigator and GSK Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors.

•A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy [for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 milli-International units/milliliter (MIU/mL) and estradiol < 40 picogram (pg)/mL (<147 picomole/Litre [pmol/L]) is confirmatory].

•Body weight >= 50 kilogram (kg) and body mass index (BMI) within the range 19-32 kg/square meter (m^2) (inclusive).

•Based on single QT duration corrected for heart rate by Fridericia's formula (QTcF): QTcF <450millisecond (msec); or QTcF <480 msec in subjects with right bundle branch block.

•Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Exclusion criteria

Criteria Based Upon Medical History

•Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), or prior cholecystectomy.

•History of asthma, anaphylaxis or anaphylactoid reactions, or severe allergic responses.

•Lifetime history of suicide attempt or active suicidal ideation within the past six months.

•Current major depressive episode or a previous episode of depression requiring medical intervention.

•History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical research unit uses heparin to maintain intravenous cannula patency).

•History of sensitivity to compounds with a chemical structure related to rilapladib or itraconazole, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.

•Any contraindications for itraconazole administration.

•Requiring the use of oral or injectable strong Cytochrome P450 3A4 (CYP3A4) inhibitors or use of other CYP3A4 inhibitors/inducers within 14 days prior to dosing.

•Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.

•History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 gram (g) of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

Criteria Based Upon Diagnostic Assessments

•A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody result, or positive test for Human Immunodeficiency Virus (HIV) antibody.

•Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

•A positive pre-study drug or alcohol screen.

Other Criteria

•Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

•The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

•Previous participation in this study.

•Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

•Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices within 7 days prior to the first dose of study medication until collection of the final pharmacokinetic sample.

Endpoints (15)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Safety / tolerability / PK

15 endpoints

Primary/protocol endpoint

Maximum observed concentration (Cmax), time of occurrence of Cmax (Tmax), area under the concentration-time curve over the dosing interval (AUC(0-Tau)) of rilapladib parent compound after single and repeat dosing, in part A of the study.

Time frame:Day (D)1: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 18, 24 hours (hrs) post-dose, and D14: pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 32, 48 (D16), 96 (D18), 144 (D20), 240 (D24) and 336 (D28) hrs post-dose. Pre-dose on Days 11, 12 and 13

concentration, descriptive

Primary/protocol endpoint

Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity)), and terminal phase half-life (T1/2) of rilapladib after repeat dosing, in part A of the study

Time frame:D1: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 18, 24 hrs post-dose, and D14: pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 32, 48 (D16), 96 (D18), 144 (D20), 240 (D24) and 336 (D28) hrs post-dose. Pre-dose on Days 11, 12 and 13

concentration, descriptive

Primary/protocol endpoint

Cmax, Tmax, AUC(0-tau), and area under the concentration-time curve from time zero (pre-dose) to time of last quantifiable concentration (AUC(0-t)) of SB-664601 and GSK1174379 after single and repeat dosing, in part A of the study

concentration, descriptive

Primary/protocol endpoint

AUC(0-infinity) and T1/2 of SB-664601 and GSK1174379 after repeat dosing, as data permit, in part A of the study.

concentration, descriptive

Primary/protocol endpoint

AUC(0 infinity), AUC(0 t), and Cmax of rilapladib alone and in the presence of itraconazole in part B of the study.

Time frame:D1 : Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 32, 48 (D3), 96 (D5), 144 (D7) hours post dose, and on D 11: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 32, 48 (D13), 96 (D15), 144 (D17) hours post dose

concentration, descriptive

Secondary/protocol endpoint

Safety and tolerability of repeat oral doses of rilapladib 250 mg assessed by adverse events (AEs), in part A of the study.

Time frame:Up to Day 38

event count, event

Secondary/protocol endpoint

Safety and tolerability of repeat oral doses of rilapladib 250 mg assessed by 12-lead electrocardiogram (ECG) parameters, in part A of the study.

Time frame:Up to Day 38

descriptive

Secondary/protocol endpoint

Safety and tolerability of repeat oral doses of rilapladib 250 mg assessed by measuring vital signs, in part A of the study.

Time frame:Up to Day 38

descriptive

Secondary/protocol endpoint

Safety and tolerability of repeat oral doses of rilapladib 250 mg assessed by laboratory tests, in part A of the study.

Time frame:Up to Day 38

descriptive

Secondary/protocol endpoint

Tmax and T1/2 of rilapladib alone and in the presence of itraconazole, in part B of the study.

concentration, descriptive

Secondary/protocol endpoint

AUC(0-infinity), AUC(0-t), Cmax, Tmax and T1/2 of rilapladib metabolites, SB-664601 and GSK1174379, alone and in the presence of itraconazole, in part B of the study.

concentration, descriptive

Secondary/protocol endpoint

Safety and tolerability of single oral dose of rilapladib 25 mg when dosed alone and concomitantly with itraconazole, assessed by AEs, in part B of the study.

Time frame:Up to Day 27

descriptive

Secondary/protocol endpoint

Safety and tolerability of single oral dose of rilapladib 25 mg when dosed alone and concomitantly with itraconazole, assessed using ECG parameters, in part B of the study.

Time frame:Up to Day 27

ratio, event

Secondary/protocol endpoint

Safety and tolerability of single oral dose of rilapladib 25 mg when dosed alone and concomitantly with itraconazole, assessed as vital signs, in part B of the study.

Time frame:Up to Day 27

descriptive

Secondary/protocol endpoint

Safety and tolerability of single oral dose of rilapladib 25 mg when dosed alone and concomitantly with itraconazole, assessed by laboratory tests, in part B of the study.

Time frame:Up to Day 27

descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.