Positron Emission Tomography (PET) Study to Evaluate Biodistribution of [11C]-GSK2256098 in Healthy Subjects and Idiopathic Pulmonary Arterial Hypertension (PAH) Patients

NCT02551653 | Completed Phase 1 Results

• 1 other identifier: 204746
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

Pulmonary arterial hypertension (PAH) involves the narrowing of blood vessels connected to and within the lungs. Focal adhesion kinase (FAK) is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes which leads to stiffening and thickening of blood vessels in lungs. This further increases the blood pressure within the lungs and impairs their blood flow. This study aims to demonstrate biodistribution of FAK inhibitor, GSK2256098, in cardiopulmonary sites i.e. heart and lung tissues. The uptake of 11C-radiolabelled GSK2256098 within the lung and / or heart of healthy subjects and idiopathic pulmonary arterial hypertension (iPAH) patients will be assessed using Positron Emission Tomography (PET). Based on study results the decision as to whether a follow-on phase 2 trial should be initiated to investigate the therapeutic utility of GSK2256098 in iPAH will be decided. Sufficient number of subjects will be screened (up to 30 days prior to scan) to enrol 12 healthy subjects and 12 PAH patients in the study. Enrolled subjects will receive a microdose of \[11C\]-GSK2256098 on a scanning day which will be followed by the follow-up visit (2-4 weeks post-last dose).

Conditions

Hypertension, Pulmonary

Keywords

Idiopathic Pulmonary Arterial Hypertension; Biodistribution; Positron Emission Tomography; [11C]-GSK2256098; Healthy subjects

Outcome Measures

Primary Outcomes (2)

• Volume of Distribution of Radiolabeled GSK2256098 Measured by PET Scan

  The PET scan was acquired to measure the uptake of radiolabeled GSK2256098 in the heart and lungs, assessed as the volume of distribution (VT). The analysis was performed on Safety Population which comprised of all participants who received a microdose of study treatment.

  Day 1

• Standardized Uptake Values (SUV) of Radiolabeled GSK2256098 Measured by PET Scan

  The PET scan was acquired to measure the uptake of radiolabeled GSK2256098 in the heart and lungs, assessed as the mean standardized uptake value (SUV) averaged over the 60 minute period between 30 and 90 minutes. The analysis was performed on Safety Population which comprised of all participants who received a microdose of study treatment.

  Day 1

Study Arms (1)

[11C]-GSK2256098

EXPERIMENTAL

Subjects will receive single IV bolus injection of \[11C\]-GSK2256098 over about 30 seconds. Each unit dose will contain up to 500 millibecquerel (MBq) of \[11C\]-GSK2256098 with maximum \[11C\]-GSK2256098 mass \<=10 microgram (mcg).

Drug: [11C]-GSK2256098 500 MBq

Interventions

[11C]-GSK2256098 500 MBq DRUG

\[11C\]-GSK2256098 injection will be provided as IV infusion, 20 mL, containing up to 5% ethanol in saline.

[11C]-GSK2256098

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Healthy subjects enrolled between 40 to 70 years inclusive at the time of signing the informed consent. Healthy subjects will be recruited to be age (+/-5 years) and gender matched to idiopathic PAH patients.
• Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
• Normal spirometry at Screening (forced expiratory volume in 1 second \[FEV1\] and forced vital capacity \[FVC\] \>= 80% of predicted - measurements to be taken in triplicate and the highest value must be \>= 80% of predicted).
• A subject with a clinical abnormality or laboratory parameter(s) outside the reference range for the population being studied may be included only if the investigator, in consultation with the medical monitor if deemed necessary, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Subject is ambulant and capable of attending for PET- computed tomography (CT) imaging.
• A negative Allen's test in at least one arm for arterial blood sampling (indicating adequate collateral circulation to the hand from both the radial and ulnar arteries).
• Body weight \>=50 kg and body mass index (BMI) within the range 18.5 - 35 kilogram/meter\^2 (kg/m\^2) (inclusive).
• Male or Female A. Males: Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until 3 months after the scan. In addition, they must not plan to father a child, or donate sperm, for 3 months after the scan.
• Vasectomy with documentation of azoospermia.
• Male condom plus partner use of one of the contraceptive options below:
• Contraceptive subdermal implant
• Intrauterine device or intrauterine system
• Oral Contraceptive, either combined or progestogen alone Injectable progestogen
• Contraceptive vaginal ring
• Percutaneous contraceptive patches

You may not qualify if:

• Presence or history, of any significant or uncontrolled medical condition which in the opinion of the investigator would increase the potential risk to the subject or affect the study outcomes.
• Previous pulmonary embolus
• Current or chronic history of intrinsic liver disease, or known hepatic or biliary abnormalities, including coagulation abnormalities (with the exception of Gilbert's syndrome).
• Established diagnosis of systemic hypertension or known Left Ventricular Hypertrophy (LVH).
• Estimated GFR \<60 milliliter/minute (mL/min) based on clinical chemistry.
• Use of prohibited medication as mentioned in protocol.
• Current smoker or a history of smoking within 6 months of Screening, or a total pack year history of \>5 pack years.
• \[number of pack years = (number of cigarettes per day/20) x number of years smoked\]
• Subjects that do not wish to consume alcohol by intravenous (IV) administration for personal reasons.
• History of regular alcohol consumption within 6 months of the study defined as:
• For United Kingdom (UK) sites: an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• 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 Medical Monitor, contraindicates their participation.
• Subject with QT duration corrected for heart rate by Fridericia's formula (QTcF) of \>450 milliseconds (msec) (or QTcF of \> 480 msec in subjects with Bundle Branch Block) or other 12-lead electrocardiogram (ECG) abnormalities (with the exception of right bundle-branch block) which, in the opinion of the investigator, is clinically significant (e.g. LVH) in that they may increase safety risk or affect study outcomes.
• Have donated blood or have taken part in a study of an experimental medicine in the last 3 months, or plan to do so in the 3 months after this study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

GSK Investigational Site

London, United Kingdom

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Familial Primary Pulmonary Hypertension

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2015
• First Posted: September 16, 2015
• Study Start: November 17, 2015
• Primary Completion: March 14, 2017
• Study Completion: March 14, 2017
• Last Updated: November 14, 2018
• Results First Posted: August 17, 2018

Record last verified: 2018-10

Locations

GB (2)