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Subjects will receive a single dose of GSK525762 10 mg on Day 1 followed by 200 mg Itraconazole two times a day (BID) on Day 3. On Day 4 to Day 6 inclusive subjects will receive a single dose of itraconazole 200 mg in the morning. On Day 7 subjects will receive a single dose of GSK525762 5 mg one hour after receiving 200 mg dose of itraconazole. On day 8 and 9 subjects will receive a single dose of 200 mg itraconazole in the morning.

Subjects will receive a single dose of GSK525762 10 mg on day 1 followed by 200 mg Itraconazole BID on day 3. On day 4 to day 6 inclusive subjects will receive a single dose of itraconazole 200 mg in the morning. On day 7 subjects will receive a single dose of GSK525762 5 mg or GSK525762 10 mg one hour after receiving 200 mg dose of itraconazole. On day 8 and 9 subjects will receive a single dose of 200 mg itraconazole in the morning.

Subjects will receive a single dose of GSK525762 10 mg on day 1. From day 3 to 17 inclusive, subjects will receive a single dose of 600 mg rifampicin in fasting conditions. On day 18 subjects will receive single dose of GSK525762 either 20 or 30 mg along with 600 mg dose of rifampicin. On day 19 subjects will receive a single dose of rifampicin 600 mg.

GSK525762 is available as a film-coated, white to slightly colored round, biconvex tablets with no markings. It is available in unit dose strength of 5 mg.

GSK525762 Besylate Tablets

Itraconazole is available as a clear yellow solution with unit dose strength of 10 mg/mL

Itraconazole 200 mg

Rifampicin is available as a red capsule with printed markings and as a 300 mg unit dose strength.

Rifampicin 300 mg

GSK Clinical Trials

This is a Phase I, single center, two-part, randomized, open label, cross-over study. Part 1 of this study will evaluate the PK, safety, and tolerability of GSK525762 when administered alone and when co-administered following repeat dosing of itraconazole, a known strong inhibitor of Cytochrome P450 3A4 (CYP3A4) and a Para-glycoprotein (Pgp) inhibitor. Part 1 will consist of 2 Cohorts with preliminary PK and safety data obtained from Cohort 1 informing Cohort 2. Part 2 (one Cohort) of the study will evaluate the PK, safety, and tolerability of GSK525762 when administered alone and when co-administered following repeat dosing of rifampicin, a known potent inducer of CYP3A4. In vitro inhibition data indicate CYP3A4 may be the major route of clearance for GSK525762 and co-administration of drug therapies which modulate CYP3A4 (i.e.CYP3A4 inhibitors and inducers) is likely to alter the exposure of GSK525762 (i.e. increase or decrease exposure, respectively). The data generated from this current study to justify exclusion criteria on concomitant medications which affect CYP3A4 or Pgp and also inform potential dose modification in case of co-administration with medication affecting CYP3A4 activity. All subjects will undergo a screening visit within 28 days of the first dose of study drug followed by one treatment period and a follow-up visit 7-10 days after the last dose of GSK525762. Subjects in Part 1 will participate in the study for up to 45 days and subjects in Part 2 will participate for up to 56 days.

A Cross-over Study to Evaluate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics (PK) of GSK525762 in Healthy Female Subjects of Non Child Bearing Potential

A Single Center, Two Part, Randomized, Open Label Cross-over Study to Evaluate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of GSK525762 in Healthy Female Subjects of Non Child Bearing Potential

IPD for this study is available via the Clinical Study Data Request site.

An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement will be categorized as SAE

Blood samples will be collected at screening, pre dose (Day 1), and post dose on Day 3,Day 6 and at follow-up visit to analyze platelet counts, red blood cells (RBC) count, white blood cells (WBC) count (absolute), haemoglobin, hematocrit and differential WBC count ( neutrophils, lymphocytes, monocytes, eosinophils, and basophils).

Blood samples will be collected at screening, pre dose (Day 1), and post dose on Day 3,Day 6 and at follow-up visit to analyze blood urea nitrogen (BUN), creatinine, glucose (fasting), sodium, c peptide, potassium, chloride, magnesium, ionized calcium, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase (ALP) levels, gamma-glutamyltransferase (GGT), total and direct bilirubin, total carbon dioxide, total protein and albumin

Urine samples will be collected at screening, pre dose (Day 1), and post dose on Day 3,Day 6 and at follow-up visit to analyze specific gravity, pH, glucose, protein, blood and ketone bodies by dipstick method, microscopic examination (if blood or protein is abnormal) WBCs, RBCs, hyaline casts, granular casts and cellular casts.

ECGs will be measured in supine position after 5 minutes rest using a standard 12-lead ECG machine that automatically calculates the HR and measures PR, QRS, QT and QTcF intervals.

Systolic and diastolic blood pressure will be measured on each day in supine or semi-supine position after 5 minutes rest.

Heart rate will be measured on each day in supine or semi-supine position after 5 minutes rest.

An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement will be categorized as SAE.

Blood samples will be collected at screening, pre dose (Day 1), and post dose on Day 3,Day 4, Day 17 and at follow-up to analyze platelet counts, RBC count, WBC count (absolute), haemoglobin, hematocrit and differential WBC count ( neutrophils, lymphocytes, monocytes, eosinophils, and basophils).

Blood samples will be collected at screening, pre dose (Day 1), and post dose on Day 3,Day 4, Day 17 and at follow-up visit to analyze BUN, creatinine, glucose (fasting), sodium, c peptide, potassium, chloride, magnesium, ionized calcium, AST/SGOT, ALT/SGPT, ALP levels, GGT, total and direct bilirubin, total carbon dioxide, total protein and albumin

Urine samples will be collected at screening, pre dose (Day 1), and post dose on Day 3,Day 4, Day 17 and at follow-up visit to analyze specific gravity, pH, glucose, protein, blood and ketone bodies by dipstick method, microscopic examination (if blood or protein is abnormal) WBCs, RBCs, hyaline casts, granular casts and cellular casts.

On Day 1 and Day 18 ECGs will be measured in supine position after 5 minutes rest at screening, pre-dose, 1 hr, 24 hr and 48 hrs.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Cross-over Study to Evaluate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics (PK) of GSK525762 in Healthy Female Subjects of Non Child Bearing Potential	NCT02706535	Drug Interactio... Neoplasms	GSK525762 Besyl... Itraconazole 20... Rifampicin 300 ...	18 Years - 70 Years	GlaxoSmithKline
A Cross-over Study to Evaluate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics (PK) of GSK525762 in Healthy Female Subjects of Non Child Bearing Potential	NCT02706535	Drug Interactio... Neoplasms	GSK525762 Besyl... Itraconazole 20... Rifampicin 300 ...	18 Years - 70 Years	GlaxoSmithKline

Spots Global Cancer Trial Database for rifampicin 300 mg