| CTRI Number |
CTRI/2010/091/001470 [Registered on: 22/10/2010] |
| Last Modified On: |
26/02/2013 |
| Post Graduate Thesis |
|
| Type of Trial |
BA/BE |
Type of Study
Modification(s)
|
|
| Study Design |
Non-randomized, Multiple Arm Trial |
Public Title of Study
Modification(s)
|
Study to Assess the Pharmacokinetics of GSK1278863A Co administered with a High Fat Meal or an Inhibitor of CYP2C8 (gemfibrozil) |
Scientific Title of Study
Modification(s)
|
Open Label Study to Assess the Pharmacokinetics of
GSK1278863A Coadministered with a High Fat Meal or an
Inhibitor of CYP2C8 (gemfibrozil) |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
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| Secondary ID |
Identifier |
| PHI113634 |
Protocol Number |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Dr Anil K |
| Designation |
|
| Affiliation |
|
| Address |
Head, Human Pharmacology Unit
Clinigene International Limited
Bangalore
KARNATAKA
560100
India |
| Phone |
08028082722 |
| Fax |
|
| Email |
anil.dr@clinigeneintl.com |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Anand Eswaraiah |
| Designation |
Head, Clinical Development and Regulatory Affairs |
| Affiliation |
Head, Clinical Development and Regulatory Affairs |
| Address |
Clinigene International Limited
"Clinigene House",
Tower 1, Semicon Park
Electronic City, Phase II,
Hosur Road, Bangalore - 560100, India
CliClinigene International Limited
"Clinigene House",
Tower 1, Semicon Park
Electronic City, Phase II,
Hosur Road, Bangalore - 560100, India
Bangalore
KARNATAKA
560100
India |
| Phone |
08028082728 |
| Fax |
|
| Email |
Anand.Eswaraiah@clinigeneintl.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Dr Siddangouda Patil |
| Designation |
|
| Affiliation |
|
| Address |
Clinigene International Limited
"Clinigene House",
Tower 1, Semicon Park
Electronic City, Phase II,
Hosur Road, Bangalore - 560100, India
Clinigene International Limited
"Clinigene House",
Tower 1, Semicon Park
Electronic City, Phase II,
Hosur Road, Bangalore - 560100, India
Bangalore
KARNATAKA
560100
India |
| Phone |
08028082823 |
| Fax |
|
| Email |
Siddangouda.Patil@clinigeneintl.com |
|
Source of Monetary or Material Support
Modification(s)
|
| Glaxo Smithkline, LLC
PO Box 13398, Five More Drive,
Research Triangle Park.
North-Carolina 27709-3398
USA
|
|
Primary Sponsor
Modification(s)
|
| Name |
GlaxoSmithKline |
| Address |
LLCPO Box 13398, Five More Drive, Research Triangle Park. North-Carolina 27709-3398USA |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
Details of Secondary Sponsor
Modification(s)
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|
Countries of Recruitment
Modification(s)
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Anil K |
Human Pharmacology Unit, Clinigene International Ltd. |
Clinigene International Limited,Tower 1, Semicon park, Phase II, Electronics City-560100
Bangalore
KARNATAKA |
08028082771
08028082722
anil.dr@clinigeneintl.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Independent Ethics Committee Consultants "Darussalam", 598. 2nd Cross, 3rd block Koramangala , Bangalore-560034, India |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
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|
Health Condition / Problems Studied
Modification(s)
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| Health Type |
Condition |
| Healthy Human Volunteers |
Healthy Volunteer |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Intervention |
GSK1278863A Coadministered with a High Fat Meal or an Inhibitor of CYP2C8 (gemfibrozil), and of an OATP1B1 substrate (rosuvastatin) Co-administered with GSK1278863A |
GSK1278863A 100mg, GSK1278863A 100mg + Gemfibrozil
600mg steady state, GSK1278863A 100mg + Gemfibrozil
600mg steady state, Rosuvastatin 10mg PM +
GSK1278863A 100mg AM |
| Comparator Agent |
NIL |
NIL |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
55.00 Year(s) |
| Gender |
Both |
| Details |
1. AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
2. 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 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. .
3. Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent.
4. 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 (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods, if they wish to continue their
HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks should elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
5. Male subjects must agree to use one of the contraception methods listed in protocol. This criterion must be followed from the time of the first dose of study medication until 5 terminal half-lives post-last dose.
6. Body weight ≥ 50 kg and BMI within the range 19 ? 29.9 kg/m2 (inclusive).
7. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
8. QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch
Block
|
|
| ExclusionCriteria |
| Details |
1. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening:
2. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
3. The values of hematological parameters at screening are:
? Any values outside the reference range
4. A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
5. The values of the following tests at screening are:
? Serum ferritin: outside the reference range
6. A positive test for HIV antibody.
7. Clinically significant CPK >3 X ULN or deemed clinically significant by the investigator
8. Calculated creatinine clearance: < 80 mL/min
9. Subjects with a pre-exisisting condition interfering with normal gastrointestinal anatomy or motility, and/or hepatic function-that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Examples of conditions that could interfere with normal gastriointestinal anatomy or motility include cholecystectomy, vagotomy, malabsorption, Crohn?s disease, ulcerative colitis, or celiac sprue.
10. History of regular alcohol consumption within 6 months of the study defined as:
? 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.
11. 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: 12 weeks, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
12. History of peptic ulcer disease
13. History of malignancy tumor. Non-melanoma skin cancer that has been definitely removed is allowed.
14. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
15. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John?s Wort) within 14 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.
16. 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.
17. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
18. Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
19. Lactating females.
20. Unwillingness or inability to follow the procedures outlined in the protocol.
21. Subject is mentally or legally incapacitated.
22. History of sensitivity to heparin or heparin-induced thrombocytopenia.
23. Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
24. Consumption of red wine, apples, star fruit, or citrus fruits/juices including blood oranges (with the exception of oranges, mandarins and lemons) from 7 days prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor this will not interfere with the study procedures and compromise subject safety
|
|
Method of Generating Random Sequence
Modification(s)
|
Not Applicable |
Method of Concealment
Modification(s)
|
Not Applicable |
Blinding/Masking
Modification(s)
|
Open Label |
Primary Outcome
Modification(s)
|
| Outcome |
TimePoints |
1. Plasma GSK1278863AAUC(0-∞) and Cmax.
2. Plasma rosuvastatin AUC(0-∞) and Cmax
|
GSK1278863A 48 h PK, Rosuvastatin 48 h PKb |
|
Secondary Outcome
Modification(s)
|
| Outcome |
TimePoints |
1. Plasma GSK1278863A AUC(0-t), tmax, and t1/2.
2. Plasma rosuvastatin AUC(0-t), tmax, and t1/2.
3. Safety and tolerability parameters, including adverse event, clinical laboratory, ECG, vital signs, and concurrent medication assessments
|
GSK1278863A 48 h PK, Rosuvastatin 48 h PK |
|
Target Sample Size
Modification(s)
|
Total Sample Size="46"
Sample Size from India="46"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
Phase of Trial
Modification(s)
|
Phase 1 |
Date of First Enrollment (India)
Modification(s)
|
10/11/2010 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
Estimated Duration of Trial
Modification(s)
|
Years="1"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
Publication Details
Modification(s)
|
Not Applicable |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
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GSK1278863A is a novel small molecule agent, which stimulates erythropoiesis through inhibition of EGLNs, mimicking the hypoxic state. This activity results in the accumulation of HIFα transcription factors which leads to increased transcription of HIF responsive genes including the gene responsible for the production of erythropoietin. The purpose of this study is to assess the clinical drug-drug interaction potential of GSK1278863A with medications that utilize either the OATP1B1 transporter, or are inhibitors of CYP2C8 enzyme in order to support co-administration of similar agents in later phase development. Approximately 46 subjects will be enrolled such that approximately 40 subjects complete dosing and critical assessments (20 per cohort). The objective of the PGx research (if there is a potential unexpected or unexplained variation) is to investigate a possible genetic relationship to handling or response to GSK1278863A. |