A Two-part Study to Investigate the Interaction and Pharmacokinetics of GSK2586184

• Register: ClinicalTrials.gov
• Last refreshed on: 28 June 2021
• Main ID: NCT01953835
• Date of registration: 26/09/2013
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A Two-part Study to Investigate the Interaction and Pharmacokinetics of GSK2586184
• Scientific title: A Two-part Healthy Volunteer Study to Investigate Both the Interaction of GSK2586184 With Rosuvastatin and Simvastatin and to Compare the Pharmacokinetics of Two Different Formulations of GSK2586184
• Date of first enrolment: October 4, 2013
• Target sample size: 37
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01953835
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Males and females aged between 18 and 65 years of age inclusive, at the time of
signing the informed consent. (Females are only eligible for Cohort A).

- Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and
cardiac monitoring. 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 GSK Medical Monitor agree and document that the
finding is unlikely to introduce additional risk factors and will not interfere with
the study procedures. Subjects with Hemoglobin (Hgb), Hematocrit (HCT), White blood
cells (WBC), neutrophil or platelet values outside the normal range should always be
excluded from enrolment.

- Body Mass Index (BMI) within the range 18 - 30 Kilogram per meter square (kg/m^2)
(inclusive).

- For Cohort A only, a female subject is eligible to participate if she is of
non-childbearing potential, defined as: Pre-menopausal females with a documented tubal
ligation, tubal occlusion procedure followed by a hysterosalpingogram that confirmed
bilateral tubal occlusion, bilateral salpingectomy or hysterectomy [ "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 per milliliter
mIU/mL and estradiol < 40 picogram/milliliter (pg/mL) (<147 picomole/liter is
confirmatory].

- Male subjects with female partners of child-bearing potential must agree to use one of
the contraception methods: Condom plus partner use of a highly effective contraceptive
or abstinence, defined as sexual inactivity consistent with the preferred and usual
lifestyle of the subject. This criterion must be followed from the time of the first
dose of study medication and for at least 2 weeks after their last dose.

- Normal creatinine clearance values at screening (calculated from serum creatinine by a
predicting equation using Cockcroft-Gault formula), normal serum creatinine value as
defined by the local reference laboratory, normal urine microscopy and no significant
proteinuria on dipstick testing.

- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <= 1.5 x Upper
Limit of Normal [ULN] (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is
fractionated and direct bilirubin < 35 %).

- Based on averaged QT duration corrected for heart rate by Fridericia's formula (QTcF)
values of triplicate ECGs obtained over a brief recording period: QTcF < 450
millisecond (msec); or QTcF < 480 msec in subjects with Bundle Branch Block.

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

Exclusion Criteria:

- A subject will not be eligible for inclusion in this study if any of the following
criteria apply:

Criteria Based Upon Medical Histories

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

- 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 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.

- History of sensitivity to any of the study medications, 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.

- Subjects who have taken statins and/or other Organic Anion-Transporting Polypeptide
(OATP) and Breast Cancer Resistance Protein (BCRP) sensitive substrates (e.g.
rapaglinide) in the 4 weeks prior to screening.

- A live vaccination within 4 weeks before the first dose of study medication, or a live
vaccination planned during the course of the study (until completion of the follow-up
visit).

- For Cohort A only: Any subject who has received an allogeneic bone marrow transplant
must be excluded.

Criteria Based Upon Diagnostic Assessments

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening

- 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/alcohol screen.

- Glycosylated Haemoglobin (HbA1c) result > 6.5 % (or 48 mmol/mol)

- A positive test for human immunodeficiency virus (HIV) antibody.

- 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).

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



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Drug: GSK2586184 standard formulation

Drug: Rosuvastatin

Drug: Simvastatin

Drug: GSK2586184 new formulation

Primary Outcome(s)

Cohort A: AUC (zero to infinity), AUC(0-t) and Cmax of Simvastatin/Simvastatin acid alone and in the presence of GSK2586184. [Time Frame: Days 1 and 10 (1 h pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24 and 48 hrs post-dose)]

Cohort B: AUC (zero to infinity), AUC(0-24), Tmax and Cmax of GSK2586184 (standard formulation, containing poloxamer) and GSK2586184 (new formulation, without-poloxamer). [Time Frame: Day 1, 4 (1 h pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hrs post dose) and Day 7 (1 h pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24)]

Cohort A: AUC (zero to infinity), AUC (0-t) and Cmax of Rosuvastatin alone and in the presence of GSK2586184 [Time Frame: Days 3 and 12 (1 hour (h) pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours (hrs) post-dose)]

Cohort B: AUC(zero to infinity), AUC(0-24), Tmax and Cmax of GSK2586184 (new formulation, without-poloxamer) dosed with and without food. [Time Frame: Day 1, 4 (1 h pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hrs post dose) and Day 7 (1 h pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24)]

Secondary Outcome(s)

Cohort B: AUC (zero to infinity), AUC(0-24), Cmax, Tmax and t1/2 of two metabolites of GSK2586184 (GSK2983628 and GSK3100466) [Time Frame: Day 1, 4 (1 h pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hrs post dose) and Day 7 (1 h pre-dose and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24)]

Cohort A: AUC(0-12) and Cmax of GSK2586184 at steady state [Time Frame: Day 9 (1 h pre-dose, and 0.5, 1, 2, 4, 6, 8, 10 and 12 hrs post dose)]

Cohort A: AUC (0-12) and Cmax of two metabolites of GSK2586184 (GSK2983628 and GSK3100466) at steady state [Time Frame: Day 9 (1 h pre-dose, and 0.5, 1, 2, 4, 6, 8, 10 and 12 hrs post dose)]

Secondary ID(s)

117171

Source(s) of Monetary Support

Please refer to primary and secondary sponsors