Crohn's DiseasePhase 1NCT01489943
A Study to Investigate the Effect of GSK1605786 on Hepatic Cytochrome P450, and BCRP and OATP1B1 Transport in Healthy Adult Subjects
A Phase 1 study testing GSK1605786 500 mg, Midazolam 3 mg and Pioglitazone 15 mg in people with Crohn's Disease, run by GlaxoSmithKline at 1 site in United States.
Trial summary
The purpose of this study is to test the effects of study drug (GSK1605786) on the blood levels of multiple commonly used drugs that are given to measure how your liver breaks down the study drug. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- GSK1605786 500 mg, Midazolam 3 mg and Pioglitazone 15 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Sep 2011to 10 Nov 2011
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin less than or equal to 1.5x the upper limit of normal (isolated bilirubin >1.5x the upper limit of normal 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 cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if in the opinion of the Investigator the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of; non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory].
- Body weight more than or equal to 60 kg and BMI within the range 19 - 30 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form (including participation in pharmacogenetics research).
- QTc < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
Who cannot join
- A positive pre-study Hepatitis B surface antigen or Hepatitis B core antibody or positive Hepatitis C antibody result within 3 months of screening
- Current illness or disability that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study (e.g., an unstable cardiovascular, autoimmune, renal, hepatic, pulmonary, endocrine, metabolic, gastrointestinal, haematologic, or neurological condition or mental impairment)
- Current or pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic or renal function, that could interfere with the absorption, metabolism, or excretion of the study drugs; including but not limited to liver disease and known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
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- 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: 30 days, 5 half-lives or twice the duration of the 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 [Hypericum perforatum], kava, ephedra [ma huang], gingko biloba, DHEA, vohimbe, saw palmetto, panaz ginseng, red yeast rice) 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 and through the duration of the study, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. Herbal medications include, but are not limited to: traditional Chinese, Korean and Japanese medicines, Panaz ginseng, Gingko biloba or St John's wort (Hypericum perforatum) or any Traditional Chinese herbal medicines (TCM) South Asian Ayurvedic medicine, Traditional Korean Medicines and Japanese Kampo.
- Use of aspirin, aspirin-containing compounds, salicylates or nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours of the first dose and is unwilling to abstain from use of these medications until the last pharmacokinetic sample has been collected.
- Use of liquid antacids (e.g. Maalox, Mylanta, Amphogel, milk of magnesia) or tablets (including chewable) antacids (e.g. TUMS™) within 48 hours of the first dose and is unwilling to abstain from use of these medications until the last dose of study medication.
- Use of digoxin or related cardiac glycoside (e.g digitoxin, deslanoside, lanatoside C, metildigoxin) within 7 days prior to screening and throughout the study.
- 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.
- Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. This includes chewing tobacco, Gutka, hand-rolled tobacco cigarettes, Biddis, cigars, and Snuff.
- Use of caffeine- or theobromine-containing beverages (e.g., coffee, tea, certain colas, green tea and oolong tea, Yerba Mate, Guarana, and South American cocoa) and foods (e.g., chocolate), or alcohol-containing beverages within 72 hours prior to dosing
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice, pummelos, exotic citrus fruits, grapefruit hybrids, fruit juice blends, apple or orange juice, vegetables from the mustard green family [e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard] and charbroiled meats from 7 days prior to the first dose of study medication.
- Confirmed diagnosis of coeliac disease, those who follow a gluten-free diet to manage symptoms of suspected coeliac disease and subjects with a positive serologic test for tissue Transglutaminase, tTG (to screen for undiagnosed coeliac disease).
- Active or latent tuberculosis (TB) infection: All subjects will be tested with TB skin test (Mantoux test) and those with positive test result will be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Centre, Single Sequence, Open-Label, Repeat-Dose Study to Investigate the Effect of GSK1605786 on Hepatic Cytochrome P450, and BCRP and OATP1B1 Transport in Healthy Adult Subjects
The purpose of this study is to test the effects of study drug (GSK1605786) on the blood levels of multiple commonly used drugs that are given to measure how your liver breaks down the study drug. These commonly-used drugs are midazolam, pioglitazone, omeprazole, and rosuvastatin which will determine the effect of GSK1605786 on how the body breaks down (metabolizes) these commonly-used drugs. Blood samples for pharmacokinetic analysis of GSK1605786, and two metabolites, [GSK2635622 (CCX062) and GSK2656694 (CCX304)] and four probe substrates will be collected over a 24-hour period after administration. Safety will be assessed by the measurement of vital signs, cardiac monitoring, collection of adverse event assessments and laboratory tests.
- Conditions
- Crohn's Disease
- Being tested
- GSK1605786 500 mg, Midazolam 3 mg, Pioglitazone 15 mg, Omeprazole 40 mg, Rosuvastatin 10 mg
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1605786 500 mgDrug
Subjects will receive 500 milligram (mg) (2 doses of 250 mg) GSK1605786 hard gelatin capsules twice daily orally on Days 5 to 14. GSK1605786 will be administered with 240 milliliter (mL) of water.
Midazolam 3 mgDrug
Subjects will receive 3 mg oral syrup of Midazolam once daily on Day 1 and Day 11. Midazolam will be administered with 240 mL of water.
Pioglitazone 15 mgDrug
Subjects will receive 15 mg tablet of pioglitazone orally once daily on Day 2 and Day 12. Pioglitazone will be administered with 240 mL of water.
Omeprazole 40 mgDrug
Subjects will receive 40 mg hard gelatin capsules of Omeprazole once daily on Days 3 and 13. Omeprazole will be administered with 240 mL of water.
Rosuvastatin 10 mgDrug
Subjects will receive 10 mg tablet of Rosuvastatin orally once daily on Days 4 and 14. Rosuvastatin will be administered with 240 mL of water.
| Study group | Role | What they receive |
|---|---|---|
| All subjects receiving treatment | Experimental | During the treatment subjects will receive Midazolam 3 mg on Day 1, Pioglitazone 15 mg on Day 2, Omeprazole 40 mg on Day 3, Rosuvastatin 10 mg on Day 4, GSK1605786 500 mg twice daily (BID) from Day 5 to 10, GSK1605786 500 mg BID + Midazolam 3 mg on Day 11, GSK1605786 500 mg BID + Pioglitazone 15 mg on Day 12, GSK1605786 500 mg BID + Omeprazole 40 mg on Day 12, GSK1605786 500 mg BID + Rosuvastatin 10 mg on Day 14 as single sequence. Receives: Drug: GSK1605786 500 mg; Drug: Midazolam 3 mg; Drug: Pioglitazone 15 mg; Drug: Omeprazole 40 mg; Drug: Rosuvastatin 10 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
To investigate the potential of GSK1605786 to inhibit or induce drug metabolism via various CYP enzymes
Midazolam AUC(0-infinity) following oral administration of midazolam alone (Day 1) and in combination with GSK1605786 (Day 11).Pioglitazone AUC(0-infinity) following oral administration of pioglitazone alone (Day 2) and in combination with GSK1605786 (Day 12).Omeprazole and 5-hydroxyomeprazole AUC(0-infinity) following oral administration of omeprazole alone (Day 3) and in combination with GSK1605786 (Day 13).
Measured: 16 Days
To investigate the potential of GSK1605786 to inhibit the BCRP and/or OATP1B1 transporters
Rosuvastatin AUC(0-infinity) following oral administration of rosuvastatin alone (Day 4) and in combination with GSK1605786 (Day 14).
Measured: 16 Days
Secondary outcomes (2)
To assess the safety and tolerablity of repeat oral doses of GSK1605786
Safety and tolerability during dosing with GSK1605786, alone and in combination with the various probe substrates. As assessed by adverse events, changes in vital signs, ECG, and hematology, clinical chemistry and urinalysis tests.
Measured: 21 Days
To determine the exposure of two metabolites, GSK2635622 (CCX062) and GSK2656694 (CCX304), relative to GSK1605786 (parent compound) following single and repeat administration of GSK1605786.
Pharmacokinetic parameters [AUC(0-infinity), AUC(0-t), AUC(0-tau), Cmax, tmax, and half-life (t1/2)] of GSK1605786 after single and repeat administration of GSK1605786. Pharmacokinetic parameters [AUC(0-infinity), AUC(0-t), AUC(0-tau), Cmax, tmax, and half-life (t1/2)] of two metabolites of GSK1605786, GSK2635622 (CCX062) and GSK2656694 (CCX304) following single and repeat administration of GSK1605786.
Measured: 16 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2011 (estimated)
- Study start19 Sep 2011
- Primary completion10 Nov 2011
- Study completion10 Nov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn's DiseaseStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 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
- NCT01489943
- Sponsor's protocol ID
- 114671
- Status last verified
- Jul 2017
- First submitted
- 1 Dec 2011
- Last updated
- 25 Jul 2017
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Centre, Single Sequence, Open-Label, Repeat-Dose Study to Investigate the Effect of GSK1605786 on Hepatic Cytochrome P450, and BCRP and OATP1B1 Transport in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT01489943
- Acronym / sponsor ID
- 114671
- Conditions
- Crohn's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 19 Sep 2011 (actual)
- Primary completion
- 10 Nov 2011 (actual)
- Study completion
- 10 Nov 2011 (actual)
- First posted
- 12 Dec 2011 (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.
The purpose of this study is to test the effects of study drug (GSK1605786) on the blood levels of multiple commonly used drugs that are given to measure how your liver breaks down the study drug. These commonly-used drugs are midazolam, pioglitazone, omeprazole, and rosuvastatin which will determine the effect of GSK1605786 on how the body breaks down (metabolizes) these commonly-used drugs. Blood samples for pharmacokinetic analysis of GSK1605786, and two metabolites, [GSK2635622 (CCX062) and GSK2656694 (CCX304)] and four probe substrates will be collected over a 24-hour period after administration. Safety will be assessed by the measurement of vital signs, cardiac monitoring, collection of adverse event assessments and laboratory tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All subjects receiving treatment | Experimental | Drug: GSK1605786 500 mg, Drug: Midazolam 3 mg, Drug: Pioglitazone 15 mg, Drug: Omeprazole 40 mg, Drug: Rosuvastatin 10 mgDuring the treatment subjects will receive Midazolam 3 mg on Day 1, Pioglitazone 15 mg on Day 2, Omeprazole 40 mg on Day 3, Rosuvastatin 10 mg on Day 4, GSK1605786 500 mg twice daily (BID) from Day 5 to 10, GSK1605786 500 mg BID + Midazolam 3 mg on Day 11, GSK1605786 500 mg BID + Pioglitazone 15 mg on Day 12, GSK1605786 500 mg BID + Omeprazole 40 mg on Day 12, GSK1605786 500 mg BID + Rosuvastatin 10 mg on Day 14 as single sequence. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin less than or equal to 1.5x the upper limit of normal (isolated bilirubin >1.5x the upper limit of normal 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 cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if in the opinion of the Investigator the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of; non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory].
- Body weight more than or equal to 60 kg and BMI within the range 19 - 30 kg/m2 (inclusive).
Key exclusion criteria (24 listed)
- A positive pre-study Hepatitis B surface antigen or Hepatitis B core antibody or positive Hepatitis C antibody result within 3 months of screening
- Current illness or disability that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study (e.g., an unstable cardiovascular, autoimmune, renal, hepatic, pulmonary, endocrine, metabolic, gastrointestinal, haematologic, or neurological condition or mental impairment)
- Current or pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic or renal function, that could interfere with the absorption, metabolism, or excretion of the study drugs; including but not limited to liver disease and known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
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 |
|---|---|---|
| GSK1605786 500 mgSubjects will receive 500 milligram (mg) (2 doses of 250 mg) GSK1605786 hard gelatin capsules twice daily orally on Days 5 to 14. GSK1605786 will be administered with 240 milliliter (mL) of water. | Drug | All subjects receiving treatment |
| Midazolam 3 mgSubjects will receive 3 mg oral syrup of Midazolam once daily on Day 1 and Day 11. Midazolam will be administered with 240 mL of water. | Drug | All subjects receiving treatment |
| Pioglitazone 15 mgSubjects will receive 15 mg tablet of pioglitazone orally once daily on Day 2 and Day 12. Pioglitazone will be administered with 240 mL of water. | Drug | All subjects receiving treatment |
| Omeprazole 40 mgSubjects will receive 40 mg hard gelatin capsules of Omeprazole once daily on Days 3 and 13. Omeprazole will be administered with 240 mL of water. | Drug | All subjects receiving treatment |
| Rosuvastatin 10 mgSubjects will receive 10 mg tablet of Rosuvastatin orally once daily on Days 4 and 14. Rosuvastatin will be administered with 240 mL of water. | Drug | All subjects receiving treatment |
Primary outcome
To investigate the potential of GSK1605786 to inhibit or induce drug metabolism via various CYP enzymes
Time frame: 16 Days
Midazolam AUC(0-infinity) following oral administration of midazolam alone (Day 1) and in combination with GSK1605786 (Day 11).Pioglitazone AUC(0-infinity) following oral administration of pioglitazone alone (Day 2) and in combination with GSK1605786 (Day 12).Omeprazole and 5-hydroxyomeprazole AUC(0-infinity) following oral administration of omeprazole alone (Day 3) and in combination with GSK1605786 (Day 13).
To investigate the potential of GSK1605786 to inhibit the BCRP and/or OATP1B1 transporters
Time frame: 16 Days
Rosuvastatin AUC(0-infinity) following oral administration of rosuvastatin alone (Day 4) and in combination with GSK1605786 (Day 14).
2 secondary outcomes
To assess the safety and tolerablity of repeat oral doses of GSK1605786
Time frame: 21 Days
To determine the exposure of two metabolites, GSK2635622 (CCX062) and GSK2656694 (CCX304), relative to GSK1605786 (parent compound) following single and repeat administration of GSK1605786.
Time frame: 16 Days
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 25 Jul 2017.
- Results for study 114671 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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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 GSK1605786 500 mg, Midazolam 3 mg and Pioglitazone 15 mg in people with Crohn's Disease, run by GlaxoSmithKline at 1 site in United States.
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 7 inclusion and 24 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 25 Jul 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 States. 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?
To investigate the potential of GSK1605786 to inhibit or induce drug metabolism via various CYP enzymes (time frame: 16 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Jul 2017.