Pulmonary Disease, Chronic ObstructivePhase 1NCT01209052

First Time in Human Study With GSK1325756

A Phase 1 study testing GSK1325756 in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study aims to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single, oral ascending doses, and repeat oral doses of GSK1325756 administered to healthy adult male volunteers. This study is the First Time in Human study for GSK1325756. Read more about this study

Who is it for?: Ages 18 to 65 years, men onlyHealthy volunteers can take part
Conditions the study is for: Pulmonary Disease, Chronic Obstructive
What is being tested?: GSK1325756
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 58 participants
Where: 1 siteUnited Kingdom
Study dates: 15 Oct 2009to 2 Mar 2010
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
Men only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Aspartate Transaminase (AST), Alanine Transaminase (ALT), alkaline phosphatase and bilirubin ≤ 1.5x Upper Limit of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and Electrocardiogram (ECG). A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Males between 18 and 65 years of age inclusive, at the time of signing the informed consent.
Subjects must agree to use one of the contraception methods listed below:
To prevent pregnancy in a female partner or to prevent exposure of any partner to the investigational product from a male subject's semen, male subjects must use one of the following contraceptive methods:
Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

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Condom (during non-vaginal intercourse with any partner - male or female) OR
Condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) (during sexual intercourse with a female) This criterion must be followed from the time of the first dose of study medication until at least 3-months post-last dose of study drug.
Body weight ≥ 60 kilograms (kg) and Body Mass Index (BMI) within the range 19 - 31 kilogrammes per square metre (kg/m-2) (inclusive)
12-lead ECG without any clinically significant abnormality as judged by the Investigator, and average QTcB or QTcF (ECG paramaters) < 450 msec
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Able to complete all study procedures and planned treatment periods.

Who cannot join

Cotinine or Exhaled Breath Carbon Monoxide (CO) Test indicative of current smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
A neutrophil count at screening of < 2 x 10(9) per litre (/L)
A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Significant cardiac, pulmonary, metabolic, renal, gastrointestinal or other conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as participant in this trial
A positive pre-study drug/alcohol screen.

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A positive test for HIV antibody.
History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males. One unit is equivalent to 8 grams of alcohol: a half-pint (~240 milliLitres(mL)) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
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: 3 months, 5 half-lives or twice the duration of the expected 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.
Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. Prescription and non-prescription non-steroidal anti-inflammatory drugs are not permitted.
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.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
Subject is mentally or legally incapacitated.
Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
London, NW10 7EW

Other trials in United Kingdom

About this study

Official title: A Single-centre, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerabilty, Pharmacokinetics, and Pharmacodynamics of Single, Oral, Ascending Doses and Repeat Oral Doses of GSK1325756 in Healthy Male Subjects.

Read the detailed description

This study will evaluate the safety, tolerability, pharmacokinetics(PK) and pharmacodynamics (PD) of single and repeat oral doses of GSK1325756 in healthy, male volunteer subjects, including the assessment of the effect of GSK1325756 on ex vivo 'C-X-C Motif Ligand 1' (CXCL1)-induced 'Cluster of Differentiation 11b' (CD11b) cell surface expression on peripheral blood neutrophils. Selective antagonism of the interaction between 'C-X-C Receptor Type 2' (CXCR2) and its various chemokine ligands provides a potential strategy for reducing the underlying inflammation that contributes to the progression of Chronic Obstructive Pulmonary Disease (COPD). This study is the first administration of GSK1325756 to humans and will be conducted in four cohorts.

Cohorts 1 and 2 will comprise of a double-blind, placebo-controlled, single dose escalation of GSK132576 in healthy adult males in two interlocking cohorts.

The data generated from this single dose escalation component of the study (safety, tolerability, and where applicable, PK profile, and, if available, PD data) will enable decisions regarding progression from one to dose the next higher dose later within Cohorts 1 and 2. This data will also be reviewed in decisions regarding study progression to repeat dosing in Cohorts 3 and 4, and the most suitable doses of GSK1325756 that should be selected for these repeat dose cohorts.

Conditions: Pulmonary Disease, Chronic Obstructive
Being tested: GSK1325756, Placebo
Keywords: COPD, CXCR2 inhibitor
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK1325756Drug
Drug will be orally administered in varying amounts over varying time periods as detailed in the 'arms' section.
PlaceboOther
Placebo will be orally administered to at least 4 subjects in each treatment period of each cohort. In each sequence in each cohort, all subjects will receive one dose of placebo.

Study groups in NCT01209052
Study group	Role	What they receive
COHORT 1	Experimental	Interlocking design with Cohort 2. Single dose; treatment period over 2 days such that two subjects will receive GSK1325756 and at least one subject will receive placebo on Day 1. The remaining subjects will be dosed on day 2 of each treatment period assuming adequate safety from Day 1. Placebo and an escalation of GSK1325756 from 10mg, to 50mg, and 200mg, will be administered over the 6 week long treatment period allowing adequate washout period between doses. Receives: Drug: GSK1325756; Other: Placebo
COHORT 2	Experimental	Interlocking design with Cohort 1. Single dose; treatment period over 2 days such that two subjects will receive GSK1325756 and at least one subject will receive placebo on Day 1. The remaining subjects will be dosed on day 2 of each treatment period assuming adequate safety from Day 1. Placebo and an escalation of GSK1325756 from 25mg, to 100mg, and 400mg, will be administered over the 6 week long treatment period allowing adequate washout period between doses. Receives: Drug: GSK1325756; Other: Placebo
COHORT 3	Experimental	Placebo controlled, 14-day, once daily, repeat-dose evaluation with one selected dose of GSK1325756 in 14 subjects. Dose selection based on review of safety and tolerability data from cohorts 1 and 2. Receives: Drug: GSK1325756; Other: Placebo
COHORT 4	Experimental	Placebo controlled, 14-day, once daily, repeat-dose evaluation with a higher selected dose of GSK1325756 in 14 subjects. Dose selection based on review of safety and tolerability data from cohort 3. Receives: Drug: GSK1325756; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety and tolerabilty of GSK1325756 as assessed by clinical monitoring of blood pressure, pulse rate, ECG, and laboratory data, as well as reporting of AEs.
Measured: Study duration

Secondary outcomes (4)

Area under the blood concentration-time curve, Maximum Concentration (Cmax), Time to Cmax (Tmax), terminal half-life and oral clearance of GSK1325756 following the administration of single escalating oral doses of GSK1325756 in healthy adult subjects.
Measured: Study duration
Area under the blood drug concentration-time curve, trough 24-hour Concentration (C24), Cmax, Tmax and accumulation of GSK1325756 following the administration of once daily repeat doses of two selected doses of GSK1325756 for 14 days in healthy subjects.
Measured: Study duration
Flow cytometric quantification of CXCL1-induced CD11b cell surface expression on peripheral blood neutrophils ex vivo following the administration of single and repeat oral doses of GSK1325756 in healthy adult subjects
Measured: Study duration
PK-PD model of the relationship between the blood concentration of GSK1325756 and CXCL1-induced CD11b cell surface expression on neutrophils ex vivo following the administration of single and repeat oral doses of GSK1325756 in healthy adult subjects
Measured: Study duration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Oct 20092 Mar 2010

First posted24 Sep 2010 (estimated)
Study start15 Oct 2009
Primary completion2 Mar 2010
Study completion2 Mar 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 58 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01209052
Sponsor's protocol ID: 112483
Status last verified: Jun 2017
First submitted: 23 Sep 2010
Last updated: 14 Jun 2017
Results posted: No
Data monitoring committee: No
Individual data sharing: Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

Miller BE, Mistry S, Smart K, Connolly P, Carpenter DC, Cooray H, Bloomer JC, Tal-Singer R, Lazaar AL. The pharmacokinetics and pharmacodynamics of danirixin (GSK1325756)--a selective CXCR2 antagonist --in healthy adult subjects. BMC Pharmacol Toxicol. 2015 Jun 20;16:18. doi: 10.1186/s40360-015-0017-x.
PubMed 26092545

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single-centre, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerabilty, Pharmacokinetics, and Pharmacodynamics of Single, Oral, Ascending Doses and Repeat Oral Doses of GSK1325756 in Healthy Male Subjects.
ClinicalTrials.gov ID: NCT01209052
Acronym / sponsor ID: 112483
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: COPD, CXCR2 inhibitor
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 58 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 15 Oct 2009 (actual)
Primary completion: 2 Mar 2010 (actual)
Study completion: 2 Mar 2010 (actual)
First posted: 24 Sep 2010 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Cohorts 1 and 2 will comprise of a double-blind, placebo-controlled, single dose escalation of GSK132576 in healthy adult males in two interlocking cohorts.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
COHORT 1	Experimental	Drug: GSK1325756, Other: PlaceboInterlocking design with Cohort 2. Single dose; treatment period over 2 days such that two subjects will receive GSK1325756 and at least one subject will receive placebo on Day 1. The remaining subjects will be dosed on day 2 of each treatment period assuming adequate safety from Day 1. Placebo and an escalation of GSK1325756 from 10mg, to 50mg, and 200mg, will be administered over the 6 week long treatment period allowing adequate washout period between doses.
COHORT 2	Experimental	Drug: GSK1325756, Other: PlaceboInterlocking design with Cohort 1. Single dose; treatment period over 2 days such that two subjects will receive GSK1325756 and at least one subject will receive placebo on Day 1. The remaining subjects will be dosed on day 2 of each treatment period assuming adequate safety from Day 1. Placebo and an escalation of GSK1325756 from 25mg, to 100mg, and 400mg, will be administered over the 6 week long treatment period allowing adequate washout period between doses.
COHORT 3	Experimental	Drug: GSK1325756, Other: PlaceboPlacebo controlled, 14-day, once daily, repeat-dose evaluation with one selected dose of GSK1325756 in 14 subjects. Dose selection based on review of safety and tolerability data from cohorts 1 and 2.
COHORT 4	Experimental	Drug: GSK1325756, Other: PlaceboPlacebo controlled, 14-day, once daily, repeat-dose evaluation with a higher selected dose of GSK1325756 in 14 subjects. Dose selection based on review of safety and tolerability data from cohort 3.

Who may qualify

Ages: 18 to 65 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Aspartate Transaminase (AST), Alanine Transaminase (ALT), alkaline phosphatase and bilirubin ≤ 1.5x Upper Limit of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and Electrocardiogram (ECG). A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Males between 18 and 65 years of age inclusive, at the time of signing the informed consent.
Subjects must agree to use one of the contraception methods listed below:
To prevent pregnancy in a female partner or to prevent exposure of any partner to the investigational product from a male subject's semen, male subjects must use one of the following contraceptive methods:

Key exclusion criteria (15 listed)

Cotinine or Exhaled Breath Carbon Monoxide (CO) Test indicative of current smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
A neutrophil count at screening of < 2 x 10(9) per litre (/L)
A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Significant cardiac, pulmonary, metabolic, renal, gastrointestinal or other conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as participant in this trial

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK1325756Drug will be orally administered in varying amounts over varying time periods as detailed in the 'arms' section.	Drug	COHORT 1, COHORT 2, COHORT 3, COHORT 4
PlaceboPlacebo will be orally administered to at least 4 subjects in each treatment period of each cohort. In each sequence in each cohort, all subjects will receive one dose of placebo.	Other	COHORT 1, COHORT 2, COHORT 3, COHORT 4

Primary outcome

Safety and tolerabilty of GSK1325756 as assessed by clinical monitoring of blood pressure, pulse rate, ECG, and laboratory data, as well as reporting of AEs.
Time frame: Study duration

4 secondary outcomes

Area under the blood concentration-time curve, Maximum Concentration (Cmax), Time to Cmax (Tmax), terminal half-life and oral clearance of GSK1325756 following the administration of single escalating oral doses of GSK1325756 in healthy adult subjects.
Time frame: Study duration
Area under the blood drug concentration-time curve, trough 24-hour Concentration (C24), Cmax, Tmax and accumulation of GSK1325756 following the administration of once daily repeat doses of two selected doses of GSK1325756 for 14 days in healthy subjects.
Time frame: Study duration
Flow cytometric quantification of CXCL1-induced CD11b cell surface expression on peripheral blood neutrophils ex vivo following the administration of single and repeat oral doses of GSK1325756 in healthy adult subjects
Time frame: Study duration
PK-PD model of the relationship between the blood concentration of GSK1325756 and CXCL1-induced CD11b cell surface expression on neutrophils ex vivo following the administration of single and repeat oral doses of GSK1325756 in healthy adult subjects
Time frame: Study duration

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2017.
Derived from this study: PubMed 26092545Miller BE, Mistry S, Smart K, Connolly P, Carpenter DC, Cooray H, Bloomer JC, Tal-Singer R, Lazaar AL. The pharmacokinetics and pharmacodynamics of danirixin (GSK1325756)--a selective CXCR2 antagonist --in healthy adult subjects. BMC Pharmacol Toxicol. 2015 Jun 20;16:18. doi: 10.1186/s40360-015-0017-x.
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
Results for study 112483 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK1325756 in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and tolerabilty of GSK1325756 as assessed by clinical monitoring of blood pressure, pulse rate, ECG, and laboratory data, as well as reporting of AEs. (time frame: Study duration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01209052, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2017; AzTrials last refreshed its copy on 3 Nov 2026.