CholestasisPhase 1NCT02801981
Dose-escalation Study of GSK2330672 in Japanese Healthy Male Volunteers
A Phase 1 study testing GSK2230672 in people with Cholestasis, run by GlaxoSmithKline at 1 site in Japan.
Trial summary
This study will be the first to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics following single dose of 10 milligrams (mg) to 180 mg of GSK2330672 in Japanese healthy subjects. Read more about this study
- Who is it for?
- Ages 20 to 64 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Cholestasis
- What is being tested?
- GSK2230672
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteJapan
- Study dates
- Jun 2016to Aug 2016
- 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 20 to 64 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Japanese male aged between 20 and 64 years of age inclusive, at the time of signing the informed consent
- Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECG. 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 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.
- Regular bowel movement >=1 per two days.
- Body weight >= 50 kilogram and body mass index (BMI) is more than or equal to 18.5 kilogram / square meter (kg/m^2) and less than 25.0 kg/m^2
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
Who cannot join
- Alanine transaminase (ALT) and/or bilirubin >1.5x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome)
- QT interval corrected for heart rate according to Fridericia's formula (QTcF) > 450 millisecond (msec)
- Current or chronic history of inflammatory bowel disease, chronic diarrhea, Crohn's disease or malabsorption syndromes.
- Current or chronic history of cholelithiasis, inflammatory gall bladder disease, cholestatic liver injury, and cholecystecomy.
- Fecal occult blood test positive at screening.
Show all 16Show fewer
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (includes St. John's Wort) within 14 days or 5 half-lives, whichever is longer, prior to the first dose of study medication.
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks. One drink is equivalent to 12 grams (g) of alcohol: 350 millilitre (mL) of beer, 150 mL of wine or 45 mL of 80 proof distilled spirits.
- History or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- 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
- A positive pre-study syphilis, Hepatitis B surface antigen, Hepatitis C antibody, Human Immunodeficiency Virus (HIV) antigen antibody or Human T-cell Lymphotropic Virus-1 (HTLV-1) antibody result of screening
- A positive pre-study urine drug screen.
- History of donation of blood or blood products >= 400 mL within 3 months or >= 200 mL within 1 month prior to screening.
- The subject has participated in a clinical trial and has received an investigational product within four months or 5 half-lives (whichever is longer) prior to the dosing day in the current study
- Exposure to more than four new chemical entities within 12 months prior to the dosing day.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-blind, Randomized, Placebo Controlled, Dose Escalating Crossover Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Parameters of Single Doses of GSK2330672 in Japanese Healthy Male Volunteers
This study will be the first to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics following single dose of 10 milligrams (mg) to 180 mg of GSK2330672 in Japanese healthy subjects. This is a double-blind, randomized, placebo-controlled, dose-escalating and incomplete block crossover study to be conducted in 16 Japanese healthy subjects. Study will be conducted in four periods; subjects will receive either placebo or GSK2330672 (10 mg, 30 mg, 90 mg or 180 mg based on randomization) in each treatment period. Each period will be separated by washout period (at least 6 days from dosing). Total duration of study for each subject will be approximately 5 weeks from the first dosing to follow up visit.
- Conditions
- Cholestasis
- Being tested
- GSK2230672, Placebo
- Keywords
- tolerability, healthy volunteers, Cholestasis, safety
- Medical subject headings
- Cholestasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2230672Drug
It will be supplied as white to slightly colored, round, film coated tablet for oral administration containing 10 mg or 45 mg of GSK2330672.
PlaceboDrug
It will be supplied as placebo tablets (with no GSK2230672) visually matching to GSK2230672
| Study group | Role | What they receive |
|---|---|---|
| Sequence 1: GSK2230672 10mg, 30mg, 90mg, and Placebo | Experimental | Subjects will receive GSK2230672 10 mg in period 1, GSK2230672 30 mg in Period 2, GSK2230672 90 mg in Period 3 and placebo in period 4. Receives: Drug: GSK2230672; Drug: Placebo |
| Sequence 2:GSK2230672 10mg, 30mg, Placebo, and GSK2230672 90mg | Experimental | Subjects will receive GSK2230672 10 mg in period 1, GSK2230672 30 mg in Period 2, placebo in period 3, and GSK2230672 90 mg in period 4. Receives: Drug: GSK2230672; Drug: Placebo |
| Sequence 3:GSK2230672 10mg, Placebo, GSK2230672 90mg and 180mg | Experimental | Subjects will receive GSK2230672 10 mg in period 1, placebo in Period 2, GSK2230672 90 mg in Period 3 and GSK2230672 180 mg in period 4. Receives: Drug: GSK2230672; Drug: Placebo |
| Sequence 4: Placebo, GSK2230672 30mg, 90mg and 180mg | Experimental | Subjects will receive placebo in period 1, GSK2230672 30 mg in Period 2, GSK2230672 90 mg in Period 3 and GSK2230672 180 mg in period 4. Receives: Drug: GSK2230672; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects with Adverse events (AE)
Measured: Maximum of 5 weeks
Safety as assessed by blood pressure
Systolic and diastolic blood pressure will be measured on Day -1, post dose 2 hours (hrs), 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up.
Measured: Maximum of 5 weeks
Safety as assessed by heart rate
Heart rate will be measured on Day -1, post dose 2 hrs, 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up.
Measured: Maximum of 5 weeks
Safety as assessed by body temperature
Body temperature will be measured on Day -1, post dose 2 hrs, 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up.
Measured: Maximum of 5 weeks
Safety as assessed by clinical chemistry parameters
Blood sample will be collected on Day -1, at 48 hrs in each period and at follow-up
Measured: Maximum of 5 weeks
Safety as assessed by haematology
Blood sample will be collected on Day -1, at 48 hrs in each period and at follow-up
Measured: Maximum of 5 weeks
Safety as assessed by urinalysis
Sample will be collected on Day -1, at 48 hrs in each period and at follow-up
Measured: Maximum of 5 weeks
Safety as assessed by fecal occult blood
Fecal occult blood testing will be conducted on Screening (2 samples during Screening period) and each dosing period (anytime from dosing to next dose).
Measured: Maximum of 5 weeks
Safety as assessed by Electrocardiogram (ECG)
Electrocardiogram will be measured on Day -1, post dose 2 hrs, 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up.
Measured: Maximum of 5 weeks
Secondary outcomes (1)
Plasma concentration of GSK2330672
Measured: Blood samples will be collected predose and post dose at 0.5 hrs, 2 hr, 3.5 hr, 5 hr on Day 1 of each period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2016 (estimated)
- Study startJun 2016
- Primary completionAug 2016
- Study completionAug 2016
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 CholestasisStudies 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
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02801981
- Sponsor's protocol ID
- 205808
- Status last verified
- Nov 2016
- First submitted
- 13 Jun 2016
- Last updated
- 9 Nov 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Karatza E, Swift B, Carreno F, Mukherjee S, Casillas L, Lennie J, Fettiplace J, McLaughlin MM, Kremer AE. Serum bile acid change correlates with improvement in pruritus in patients with primary biliary cholangitis receiving linerixibat. Liver Int. 2024 Sep;44(9):2293-2302. doi: 10.1111/liv.15982. Epub 2024 May 23.
PubMed 38780109
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Placebo Controlled, Dose Escalating Crossover Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Parameters of Single Doses of GSK2330672 in Japanese Healthy Male Volunteers
- ClinicalTrials.gov ID
- NCT02801981
- Acronym / sponsor ID
- 205808
- Conditions
- Cholestasis
- Keywords
- tolerability, healthy volunteers, Cholestasis, safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jun 2016
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 16 Jun 2016 (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.
This study will be the first to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics following single dose of 10 milligrams (mg) to 180 mg of GSK2330672 in Japanese healthy subjects. This is a double-blind, randomized, placebo-controlled, dose-escalating and incomplete block crossover study to be conducted in 16 Japanese healthy subjects. Study will be conducted in four periods; subjects will receive either placebo or GSK2330672 (10 mg, 30 mg, 90 mg or 180 mg based on randomization) in each treatment period. Each period will be separated by washout period (at least 6 days from dosing). Total duration of study for each subject will be approximately 5 weeks from the first dosing to follow up visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Sequence 1: GSK2230672 10mg, 30mg, 90mg, and Placebo | Experimental | Drug: GSK2230672, Drug: PlaceboSubjects will receive GSK2230672 10 mg in period 1, GSK2230672 30 mg in Period 2, GSK2230672 90 mg in Period 3 and placebo in period 4. |
| Sequence 2:GSK2230672 10mg, 30mg, Placebo, and GSK2230672 90mg | Experimental | Drug: GSK2230672, Drug: PlaceboSubjects will receive GSK2230672 10 mg in period 1, GSK2230672 30 mg in Period 2, placebo in period 3, and GSK2230672 90 mg in period 4. |
| Sequence 3:GSK2230672 10mg, Placebo, GSK2230672 90mg and 180mg | Experimental | Drug: GSK2230672, Drug: PlaceboSubjects will receive GSK2230672 10 mg in period 1, placebo in Period 2, GSK2230672 90 mg in Period 3 and GSK2230672 180 mg in period 4. |
| Sequence 4: Placebo, GSK2230672 30mg, 90mg and 180mg | Experimental | Drug: GSK2230672, Drug: PlaceboSubjects will receive placebo in period 1, GSK2230672 30 mg in Period 2, GSK2230672 90 mg in Period 3 and GSK2230672 180 mg in period 4. |
Who may qualify
- Ages
- 20 to 64 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Japanese male aged between 20 and 64 years of age inclusive, at the time of signing the informed consent
- Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECG. 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 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.
- Regular bowel movement >=1 per two days.
- Body weight >= 50 kilogram and body mass index (BMI) is more than or equal to 18.5 kilogram / square meter (kg/m^2) and less than 25.0 kg/m^2
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
Key exclusion criteria (16 listed)
- Alanine transaminase (ALT) and/or bilirubin >1.5x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome)
- QT interval corrected for heart rate according to Fridericia's formula (QTcF) > 450 millisecond (msec)
- Current or chronic history of inflammatory bowel disease, chronic diarrhea, Crohn's disease or malabsorption syndromes.
- Current or chronic history of cholelithiasis, inflammatory gall bladder disease, cholestatic liver injury, and cholecystecomy.
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 |
|---|---|---|
| GSK2230672It will be supplied as white to slightly colored, round, film coated tablet for oral administration containing 10 mg or 45 mg of GSK2330672. | Drug | Sequence 1: GSK2230672 10mg, 30mg, 90mg, and Placebo, Sequence 2:GSK2230672 10mg, 30mg, Placebo, and GSK2230672 90mg, Sequence 3:GSK2230672 10mg, Placebo, GSK2230672 90mg and 180mg, Sequence 4: Placebo, GSK2230672 30mg, 90mg and 180mg |
| PlaceboIt will be supplied as placebo tablets (with no GSK2230672) visually matching to GSK2230672 | Drug | Sequence 1: GSK2230672 10mg, 30mg, 90mg, and Placebo, Sequence 2:GSK2230672 10mg, 30mg, Placebo, and GSK2230672 90mg, Sequence 3:GSK2230672 10mg, Placebo, GSK2230672 90mg and 180mg, Sequence 4: Placebo, GSK2230672 30mg, 90mg and 180mg |
Primary outcome
Number of Subjects with Adverse events (AE)
Time frame: Maximum of 5 weeks
Safety as assessed by blood pressure
Time frame: Maximum of 5 weeks
Systolic and diastolic blood pressure will be measured on Day -1, post dose 2 hours (hrs), 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up.
Safety as assessed by heart rate
Time frame: Maximum of 5 weeks
Heart rate will be measured on Day -1, post dose 2 hrs, 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up.
Safety as assessed by body temperature
Time frame: Maximum of 5 weeks
Body temperature will be measured on Day -1, post dose 2 hrs, 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up.
Safety as assessed by clinical chemistry parameters
Time frame: Maximum of 5 weeks
Blood sample will be collected on Day -1, at 48 hrs in each period and at follow-up
Safety as assessed by haematology
Time frame: Maximum of 5 weeks
Blood sample will be collected on Day -1, at 48 hrs in each period and at follow-up
Safety as assessed by urinalysis
Time frame: Maximum of 5 weeks
Sample will be collected on Day -1, at 48 hrs in each period and at follow-up
Safety as assessed by fecal occult blood
Time frame: Maximum of 5 weeks
Fecal occult blood testing will be conducted on Screening (2 samples during Screening period) and each dosing period (anytime from dosing to next dose).
Safety as assessed by Electrocardiogram (ECG)
Time frame: Maximum of 5 weeks
Electrocardiogram will be measured on Day -1, post dose 2 hrs, 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up.
1 secondary outcome
Plasma concentration of GSK2330672
Time frame: Blood samples will be collected predose and post dose at 0.5 hrs, 2 hr, 3.5 hr, 5 hr on Day 1 of each period
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 9 Nov 2016.
- Derived from this study: PubMed 38780109Karatza E, Swift B, Carreno F, Mukherjee S, Casillas L, Lennie J, Fettiplace J, McLaughlin MM, Kremer AE. Serum bile acid change correlates with improvement in pruritus in patients with primary biliary cholangitis receiving linerixibat. Liver Int. 2024 Sep;44(9):2293-2302. doi: 10.1111/liv.15982. Epub 2024 May 23.
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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 GSK2230672 in people with Cholestasis, run by GlaxoSmithKline at 1 site in Japan.
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 5 inclusion and 16 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 9 Nov 2016. 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 Japan. 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?
Number of Subjects with Adverse events (AE) (time frame: Maximum of 5 weeks). The study lists 9 primary outcomes in all. 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 NCT02801981, 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 9 Nov 2016.