First Time in Human (FTIH) Study of GSK3008348 in Healthy Volunteers and Idiopathic Pulmonary Fibrosis Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02612051
• Date of registration: 19/11/2015
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: First Time in Human (FTIH) Study of GSK3008348 in Healthy Volunteers and Idiopathic Pulmonary Fibrosis Patients
• Scientific title: A FTIH Study With GSK3008348 in Healthy Volunteers and Patients With Idiopathic Pulmonary Fibrosis
• Date of first enrolment: December 4, 2015
• Target sample size: 40
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02612051
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

United Kingdom

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

Part A:

- Male and female subjects >= 18 years at the time of signing the consent form.

Parts B and C :

- Male subjects >= 45 years and female subjects >= 55 years at the time of signing the
consent form.

Part A:

- Healthy as determined by the investigator or medically qualified designee based on a
medical evaluation including medical history, physical examination, laboratory tests,
12-lead ECG and pulmonary function tests.

- A subject with a potentially clinically significant 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 Medical Monitor if required agree
and document that the finding is unlikely to introduce additional risk factors and
will not interfere with the study procedures. Subjects with FEV1, FVC and DLCO values
outside the normal range may be included only if the investigator in consultation with
the Medical Monitor agree and document that the finding is unlikely to introduce
additional risk factors and will not interfere with the study procedures.

Parts B and C:

- Subject is ambulant and capable of attending a PET scan visit as an outpatient.

- Subjects will have a diagnosis of IPF as determined by a responsible and experienced
chest physician and based on established criteria defined by the American Thoracic
Society/European Respiratory Society Internationale Multidisciplinary Consensus
Classification of the Idiopathic Interstitial Pnuemonias.

- FVC > 50 % predicted and DLCO > 50% predicted. Following a review of the safety data
at the interim, these criteria may be altered to FVC > 50% predicted and DLCO > 40%
predicted.

Part A:

- Body weight >=50 Kilogram (kg) and BMI within the range 19.0 - 35.0 kg/meter square (m^2)
(inclusive).

Parts B and C:

- Body weight >=45 kg and BMI within the range 18.0 - 35.0 kg/m^2 (inclusive)

- Female subjects are eligible to participate if they are of non-childbearing potential
defined as premenopausal females with a documented tubal ligation or hysterectomy; or
postmenopausal defined as 12 month of spontaneous amenorrhea (in questionable cases a
blood sample with simultaneous follicle stimulating hormone (FSH) > 40
milli-international unit (MIU)/millilitre (ml) and estradiol > 141 picomole
(pmol)/litre (l) is confirmatory (as a precaution a pregnancy test is conducted prior
to dosing, a positive test leads to exclusion).

- 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 90 days after the last dose of study medication. a. Vasectomy with documentation
of azoospermia b. Male condom plus partner use of one of the contraceptive options
below: i. Contraceptive subdermal implant that meets the Standard Operating Procedure
(SOP) effectiveness criteria including a <1% rate of failure per year, as stated in
the product label ii. Intrauterine device or intrauterine system that meets the SOP
effectiveness criteria including a <1% rate of failure per year, as stated in the
product label iii. Oral Contraceptive, either combined or progestogen alone iv.
Injectable progestogen v. Contraceptive vaginal ring vi. Percutaneous contraceptive
patches This is an all-inclusive list of those methods that meet the following
GlaxoSmithKline (GSK) definition of highly effective: having a failure rate of less
than 1% per year when used consistently and correctly and, when applicable, in
accordance with the product label. For non-product methods (e.g., male sterility), the
investigator determines what is consistent and correct use. The investigator is
responsible for ensuring that subjects understand how to properly use these methods of
contraception.

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

Exclusion Criteria:

- Alanine transaminase and bilirubin >1.5x5xupper limit of normal (ULN) (isolated
bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin
<35%).

- Current or history of photosensitivity.

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

- QT interval corrected for heart rate (QTc )> 450 millisecond (msec) or QTc > 480 msec
in subjects with Bundle Branch Block

- Current upper or lower respiratory tract infection on admission to the clinical unit.

Parts B and C:

- History or suffers from claustrophobia or subject feels unable to lie flat and still
on their back for a period of up to 2 hours in the PET/ CT scanner (note, one rest
period will be allowed during the scan if required).

- Previous inclusion in a research and/or medical protocol involving nuclear medicine,
PET or radiological investigations or occupational exposure resulting in radiation
exposure greater than 10 millisievert (mSv) over the past 3 years or greater than 10
mSv in a single year including the proposed study. Clinical exposure from which the
subject receives a direct benefit is not included in these calculations.

- Subjects with current IPF exacerbation, upper or lower respiratory tract infection.

- Subjects with severe co-existent chronic obstructive pulmonary disease (COPD), for
example FEV1 < 60% predicted.

All Parts:

- Use of prohibited medication

- Subjects who are currently taking Pirfenidone or Nintedanib or who have received
Pirfenidone or Nintedanib within the 30 days prior to the first dosing day will be
excluded from the study.

- Subjects prescribed long-term continuous home oxygen therapy (those whose use of
oxygen is intermittent and for symptom relief only are not excluded)

- History of alcohol consumption regularly in excess of: An average weekly intake of >21
units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a
half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.

- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
nicotine-containing products within 3 months prior to screening.

- History of sensitivity to heparin or heparin-induced thr


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Idiopathic Pulmonary Fibrosis

Intervention(s)

Drug: Placebo Nebuliser solution

Drug: GSK3008348 Nebuliser solution

Radiation: GSK26346763: ([18F]-FBA-A20FMDV2) IV infusion

Primary Outcome(s)

Part A: Peripheral capillary oxygen saturation (SpO2) levels as a measure of safety and tolerability [Time Frame: Up to Day 33]

Part A: Taste questionnaire for taste of nebulised GSK3008348 as a measure of safety and tolerability [Time Frame: Up to Day 19]

Part A: Composite of hematology laboratory tests as a measure of safety and tolerability [Time Frame: Up to Day 33]

Part B: Composite of urinalysis laboratory tests as a measure of safety and tolerability [Time Frame: Up to Day 30]

Part B: Systolic and diastolic blood pressure as a measure of safety and tolerability [Time Frame: Up to Day 43]

Part A: FEV1 and FVC as a measure of safety and tolerability [Time Frame: Up to Day 33]

Part A: Number of participants with adverse events (AE) as a measure of safety and tolerability [Time Frame: Up to Day 33]

Part B: Changes in volume of distribution [VT]) at approximately 1 hour post-dose compared to pre-dose of [18F]-FBA-A20FMDV2 in the lung [Time Frame: Baseline (from Day 15), Up to Day 30]

Part A: Composite of clinical chemistry laboratory tests as a measure of safety and tolerability [Time Frame: Up to Day 33]

Part A: DLCO as a measure of safety and tolerability [Time Frame: Up to Day 20]

Part B: AE as a measure of safety and tolerability [Time Frame: Up to Day 43]

Part B: Composite of clinical chemistry laboratory tests as a measure of safety and tolerability [Time Frame: Up to Day 30]

Part B: Taste questionnaire for taste of nebulised GSK3008348 as a measure of safety and tolerability [Time Frame: Up to Day 29]

Part A: Pulse rate and respiratory rate as a measure of safety and tolerability [Time Frame: Up to Day 33]

Part B: FEV1 and FVC as a measure of safety and tolerability [Time Frame: Up to Day 43]

Part A: Systolic and diastolic blood pressure as a measure of safety and tolerability [Time Frame: Up to Day 33]

Part B: Composite of hematology laboratory tests as a measure of safety and tolerability [Time Frame: Up to Day 30]

Part B: Pulse rate and respiratory rate as a measure of safety and tolerability [Time Frame: Up to Day 43]

Part A: Composite of urinalysis laboratory tests as a measure of safety and tolerability [Time Frame: Up to Day 33]

Part A: ECG and Telemetry as a measure of safety and tolerability [Time Frame: Up to Day 21]

Part A: Temperature as a measure of safety and tolerability [Time Frame: Up to Day 33]

Part B: ECG and Telemetry as a measure of safety and tolerability [Time Frame: Up to Day 31]

Part B: Temperature as a measure of safety and tolerability [Time Frame: Up to Day 43]

Part B: DLCO as a measure of safety and tolerability [Time Frame: Up to Day 30]

Part C: Changes in VT at various time points post-dose compared to pre-dose of [18F]-FBA-A20FMDV2 in the lung [Time Frame: Baseline (from Day 1), Up to Day 29]

Part B: SpO2 levels as a measure of safety and tolerability [Time Frame: Up to Day 43]

Secondary Outcome(s)

Part B: Area under the curve (AUC) following single doses of GSK3008348 [Time Frame: Blood samples will be collected at pre-dose and at 5, 10, 15, 30 mins, 1, 2, 3, 4, 6, 8, 12 hours (Day 1) and 24 hours (Day 2) post-dose of each treatment period]

Part B: Tmax and t½ following single doses of GSK3008348 [Time Frame: Blood samples will be collected at pre-dose and at 5, 10, 15, 30 mins, 1, 2, 3, 4, 6, 8, 12 hours (Day 1) and 24 hours (Day 2) post-dose of each treatment period]

Part C: Systolic and diastolic blood pressure as a measure of safety and tolerability [Time Frame: Up to Day 43]

Part C: Composite of clinical chemistry laboratory tests as a measure of safety and tolerability [Time Frame: Up to Day 43]

Part C: Area under the curve (AUC) following single doses of GSK3008348 [Time Frame: Blood samples will be collected at pre-dose and post-nebulisation at 5, 10, 15, 30 mins, 1, 2, 3, 4, 6, 8, 12 hours (Day 1) and 24 hours (Day 2) post-dose of each treatment period]

Part C: Cmax following single doses of GSK3008348 [Time Frame: Blood samples will be collected at pre-dose and post-nebulisation at 5, 10, 15, 30 mins, 1, 2, 3, 4, 6, 8, 12 hours (Day 1) and 24 hours (Day 2) post-dose of each treatment period]

Part C: Composite of urinalysis laboratory tests as a measure of safety and tolerability [Time Frame: Up to Day 43]

Part C: Peripheral capillary oxygen saturation (SpO2) levels as a measure of safety and tolerability [Time Frame: Up to Day 43]

Part C: Tmax and t½ following single doses of GSK3008348 [Time Frame: Blood samples will be collected at pre-dose and post-nebulisation at 5, 10, 15, 30 mins, 1, 2, 3, 4, 6, 8, 12 hours (Day 1) and 24 hours (Day 2) post-dose of each treatment period]

Part A: Area under the curve (AUC) following single doses of GSK3008348 [Time Frame: Blood samples will be collected at pre-dose and at 5, 10, 15, 30 minutes (mins), 1, 2, 3, 4, 6, 8, 12 hours (Day 1) and 24 hours (Day 2) post-dose of each treatment period]

Part B: Changes in VT at 14-28 hours post-dose compared to pre-dose of [18F]-FBA-A20FMDV2 in the lung [Time Frame: Baseline (from Day 15), Up to Day 30]

Part B: Cmax following single doses of GSK3008348 [Time Frame: Blood samples will be collected at pre-dose and at 5, 10, 15, 30 mins, 1, 2, 3, 4, 6, 8, 12 hours (Day 1) and 24 hours (Day 2) post-dose of each treatment period]

Part A: Tmax and t½ following single doses of GSK3008348 [Time Frame: Blood samples will be collected at pre-dose and at 5, 10, 15, 30 mins, 1, 2, 3, 4, 6, 8, 12 hours (Day 1) and 24 hours (Day 2) post-dose of each treatment period]

Part C: Composite of hematology laboratory tests as a measure of safety and tolerability [Time Frame: Up to Day 43]

Part A: Cmax following single doses of GSK3008348 [Time Frame: Blood samples will be collected at pre-dose and at 5, 10, 15, 30 mins, 1, 2, 3, 4, 6, 8, 12 hours (Day 1) and 24 hours (Day 2) post-dose of each treatment period]

Part C: AE as a measure of safety and tolerability [Time Frame: Up to Day 43]

Part C: Pulse rate and respiratory rate as a measure of safety and tolerability [Time Frame: Up to Day 43]

Part C: Temperature as a measure of safety and tolerability [Time Frame: Up to Day 43]

Secondary ID(s)

200262

Source(s) of Monetary Support

Please refer to primary and secondary sponsors