Investigating The Pharmacokinetics Of An Inhaled Dose Of A New Corticosteroid In Patients With Impaired Liver Function

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Asthma

Treatments: Drug: GW685698X

Study type: Interventional

Funder types: Industry

Identifiers

NCT00419237

FFA10013

Details and patient eligibility

About

The proposed study is designed to investigate the pharmacokinetics, pharmacodynamics (as measured by serum cortisol) and safety of GW685698X in subjects with moderate hepatic impairment and in healthy subjects following a single oral inhaled dose of GW685698X. From the study results it should be possible to assess if there is an altered Risk: Benefit in patients with moderate hepatic impairment

Enrollment: 20 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion:

• Are aged between 18-70 years, inclusive.
• If Female, you must be incapable of becoming pregnant.
• Show FEV1 of more than 70% of the predicted normal at screening.
• Are able to correctly use a DISKUS at the screening visit.
• Have Body Mass Index within the range of 19-33 kg/m2 inclusive.
• Do not show a positive pre-study urine drug screen.
• Do not show a positive pre-study blood alcohol test.
• Demonstrate a clinically normal 12-lead ECG at screening.
• Do not show a positive blood test for HIV.

If you are a Healthy Volunteer you must also:

• Have no significant abnormality on clinical examination.
• Have Liver Function Tests within the reference range at screening.

If you are a Patient Volunteer you must:

• Have moderate hepatic impairment
• Have no significant abnormality on clinical examination apart from hepatic impairment.

Exclusion:

• Suffered an upper respiratory infection in the 4 weeks before the screening visit.
• Suffered a lower respiratory infection in the 6 weeks before the screening visit.
• Taken oral corticosteroids in the 8 weeks before the screening visit.
• Taken inhaled, intranasal or topical steroids in the 4 weeks before the screening visit.
• A prolonged heartbeat (QTc interval >470msec).
• High blood pressure (systolic >160mmHg or diastolic >90mmHg) or as defined by the Investigator.
• Known sensitivity to corticosteroids.
• A history of lactose intolerance.
• A history of severe milk protein allergy.
• Donated blood in the last 3 months, or more than 1500mL (1000mL if female) in the last 12 months (including the amount taken for this study).
• Participated in a clinical trial within the last 3 months where you are/were exposed to a drug or device.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

20 participants in 2 patient groups

Healthy subjects

Active Comparator group

Description:

Subjects with normal liver function test will be administered a single oral inhaled dose of 400 micrograms (mcg) GW685698X in the morning of the study day. Each healthy subject will be matched as closely as possible for age, gender, bodyweight and race to a subject with impaired liver function.

Treatment:

Drug: GW685698X

Subjects with hepatic impairment

Experimental group

Description:

Subjects with Child Pugh B hepatic dysfunction will be administered a single oral inhaled dose of 400 mcg GW685698X in the morning of the study day.

Treatment:

Drug: GW685698X