Macular DegenerationPhase 1NCT01072214
A Safety Study to Evaluate Pazopanib Eye Drops in Healthy Volunteers
A Phase 1 study testing pazopanib in people with Macular Degeneration, run by GlaxoSmithKline at 1 site in United States.
Trial summary
A study to determine the safety and tolerability of pazopanib eye drops. The study will also determine how the drug is absorbed and metabolized over time. Repeat doses of eye drops will be administered to healthy adult volunteers over a 14-day period with one additional dose given on the 15th day of the session. Read more about this study
- Who is it for?
- Ages 20 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Macular Degeneration
- What is being tested?
- pazopanib
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Mar 2010to 28 Jun 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 20 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (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 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.
- Male or female ≥ 20 to 64 years of age, 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 (<140 pmol/L) is confirmatory
- Body weight ≥ 50 kg for men and ≥ 45 kg for women and body mass index (BMI) within the range 18.5 - 32 kg/m2 (inclusive), where BMI = (weight in kg)/(height in meters)2.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Average QTcF < 450 msec or QTc < 480 msec in subjects with bundle branch block.
- Best-corrected visual acuity better than 20/80 (Snellen equivalent) in both eyes.
Who cannot join
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of clinically relevant coronary heart disease, uncontrolled hypertension, renal disease, diabetes mellitus, impaired endocrine, thyroid, or respiratory function, or psychotic mental illness
- History of any hemorrhagic event (hemoptysis, cerebral or gastrointestinal) within 6 months of screening
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months of screening.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- A positive pre-study drug/alcohol screen
Show all 24Show fewer
- A positive test for HIV antibody
- Blood pressure (SBP/DBP) > 140/90 mmHg at screening
- History of dry eye or presence of any active ocular disease at time of screening that the investigator and medical monitor agree may cause additional risk to the subject or may interfere with study assessments or endpoints
- Any eye surgery within three months prior to first dose of study medication
- Use of ocular prescription or non-prescription drugs within 7 days prior to the first dose of study medication
- Prior history of ocular allergy, unless symptom-free for at least 6 months from first dose.
- An unwillingness to refrain from wearing contact lenses during the study and up to 2 weeks before the study start
- 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
- 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
- Participation in a clinical trial where the subject has received an investigational product within 30 days, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer) prior to the first dose of study medication
- 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 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
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice within 7 days prior to the first dose of study medication
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
- Unwillingness or inability to follow the procedures outlined in the protocol
- For Cohort 3, the following additional inclusion criterion applies:
- Subject must have spent most of his or her life in Japan and not have lived outside of Japan for more than 5 years. They must have been born in Japan with four ethnic Japanese grandparents.
Trial locations and contacts
1 site in 1 country.
United States1 site
GSK Investigational Site
Glendale, California, 91206
About this study
Official title: A Randomized, Placebo-controlled, Double-masked, Parallel Group Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of Repeat Doses of Pazopanib Eye Drops in Healthy Adult Subjects
A study to determine the safety and tolerability of pazopanib eye drops. The study will also determine how the drug is absorbed and metabolized over time. Repeat doses of eye drops will be administered to healthy adult volunteers over a 14-day period with one additional dose given on the 15th day of the session. Three groups of subjects may receive either active drug or placebo (drops without drug). The first group of subjects will receive a maximum of 1.6mg of pazopanib or placebo. The dose of drug to be given to the next two groups will be determined based on the results of the first group of subjects. The last group of subjects will be of Japanese descent.
Read the detailed description
The purpose of this study is to characterize the ocular safety and tolerability, the systemic safety and tolerability, and the pharmacokinetic profile of repeat doses of a higher strength ophthalmic formulation of pazopanib, 10 mg/mL. The higher strength formulation provides an opportunity to increase the total daily dose of pazopanib administered. In this 3-cohort study, healthy adult volunteers will participate in one 14-day repeat-dose session (plus a single dose on day 15), randomized to receive either pazopanib eye drops or placebo. Subjects in cohort 1 will receive 1 drop four times daily for a calculated total daily dose of 1.6 mg. The dosage regimen for two subsequent cohorts will be determined based on the emerging safety profile. The Japanese population chosen for the third cohort will provide a safety and tolerability profile as well as the pharmacokinetic profile of pazopanib prior to further development of this formulation in Japanese patients with AMD.
- Conditions
- Macular Degeneration
- Being tested
- pazopanib, Placebo
- Keywords
- Pazopanib, Tolerability, Pharmacokinetics, GW786034, Safety
- Medical subject headings
- Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pazopanibDrug
gw786034
pazopanibDrug
gw786034
pazopanibDrug
gw786034
PlaceboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| 1.6 mg | Experimental | The actual dosage is 10 mg/ml (GW786034) given 4 times a day for a maximum daily dosage of 1.6mg Receives: Drug: pazopanib |
| TBD COHORT 2 | Experimental | Dose escalation amount to be determined (TBD) after results from Cohort 1 analyzed Receives: Drug: pazopanib |
| Placebo | Placebo comparator | Subjects will receive placebo (drops without drug). Receives: Drug: Placebo |
| TBD COHORT 3 | Experimental | Dose escalation amount to be determined (TBD) after results from Cohort 2 analyzed Receives: Drug: pazopanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical safety data from AE reporting, clinical observations, physical examinations, vital signs (blood pressure and heart rate), clinical laboratory tests including urinalysis, general ophthalmic examinations, and best-corrected visual acuity tests
Measured: 2 weeks
Primary pharmacokinetic endpoints will include: AUC(0-24), Cmax after repeat administration of pazopanib ophthalmic solution, Tmax, and trough steady-state plasma pazopanib concentration (Cτ)
Measured: 2 weeks
Secondary outcomes (1)
Secondary pharmacokinetic parameters include: area under the plasma drug concentration versus time curve [AUC(0-t)], observed accumulation ratio (Ro), and apparent terminal half-life (t1/2) after repeat administration will be analyzed
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2010 (estimated)
- Study start9 Mar 2010
- Primary completion28 Jun 2010
- Study completion28 Jun 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 Macular DegenerationStudies 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 37 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
- NCT01072214
- Sponsor's protocol ID
- 113748
- Status last verified
- Nov 2017
- First submitted
- 18 Feb 2010
- Last updated
- 14 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Singh R, Wurzelmann JI, Ye L, Henderson L, Hossain M, Trivedi T, Kelly DS. Clinical evaluation of pazopanib eye drops in healthy subjects and in subjects with neovascular age-related macular degeneration. Retina. 2014 Sep;34(9):1787-95. doi: 10.1097/IAE.0000000000000179.
PubMed 24896137
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled, Double-masked, Parallel Group Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of Repeat Doses of Pazopanib Eye Drops in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT01072214
- Acronym / sponsor ID
- 113748
- Conditions
- Macular Degeneration
- Keywords
- Pazopanib, Tolerability, Pharmacokinetics, GW786034, Safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 9 Mar 2010 (actual)
- Primary completion
- 28 Jun 2010 (actual)
- Study completion
- 28 Jun 2010 (actual)
- First posted
- 22 Feb 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.
A study to determine the safety and tolerability of pazopanib eye drops. The study will also determine how the drug is absorbed and metabolized over time. Repeat doses of eye drops will be administered to healthy adult volunteers over a 14-day period with one additional dose given on the 15th day of the session. Three groups of subjects may receive either active drug or placebo (drops without drug). The first group of subjects will receive a maximum of 1.6mg of pazopanib or placebo. The dose of drug to be given to the next two groups will be determined based on the results of the first group of subjects. The last group of subjects will be of Japanese descent.
Detailed description
The purpose of this study is to characterize the ocular safety and tolerability, the systemic safety and tolerability, and the pharmacokinetic profile of repeat doses of a higher strength ophthalmic formulation of pazopanib, 10 mg/mL. The higher strength formulation provides an opportunity to increase the total daily dose of pazopanib administered. In this 3-cohort study, healthy adult volunteers will participate in one 14-day repeat-dose session (plus a single dose on day 15), randomized to receive either pazopanib eye drops or placebo. Subjects in cohort 1 will receive 1 drop four times daily for a calculated total daily dose of 1.6 mg. The dosage regimen for two subsequent cohorts will be determined based on the emerging safety profile. The Japanese population chosen for the third cohort will provide a safety and tolerability profile as well as the pharmacokinetic profile of pazopanib prior to further development of this formulation in Japanese patients with AMD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1.6 mg | Experimental | Drug: pazopanibThe actual dosage is 10 mg/ml (GW786034) given 4 times a day for a maximum daily dosage of 1.6mg |
| TBD COHORT 2 | Experimental | Drug: pazopanibDose escalation amount to be determined (TBD) after results from Cohort 1 analyzed |
| Placebo | Placebo comparator | Drug: PlaceboSubjects will receive placebo (drops without drug). |
| TBD COHORT 3 | Experimental | Drug: pazopanibDose escalation amount to be determined (TBD) after results from Cohort 2 analyzed |
Who may qualify
- Ages
- 20 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (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 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.
- Male or female ≥ 20 to 64 years of age, 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 (<140 pmol/L) is confirmatory
- Body weight ≥ 50 kg for men and ≥ 45 kg for women and body mass index (BMI) within the range 18.5 - 32 kg/m2 (inclusive), where BMI = (weight in kg)/(height in meters)2.
Key exclusion criteria (24 listed)
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of clinically relevant coronary heart disease, uncontrolled hypertension, renal disease, diabetes mellitus, impaired endocrine, thyroid, or respiratory function, or psychotic mental illness
- History of any hemorrhagic event (hemoptysis, cerebral or gastrointestinal) within 6 months of screening
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months of screening.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
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 |
|---|---|---|
| pazopanibgw786034 | Drug | TBD COHORT 2 |
| pazopanibgw786034 | Drug | 1.6 mg |
| pazopanibgw786034 | Drug | TBD COHORT 3 |
| Placeboplacebo | Drug | Placebo |
Primary outcome
Clinical safety data from AE reporting, clinical observations, physical examinations, vital signs (blood pressure and heart rate), clinical laboratory tests including urinalysis, general ophthalmic examinations, and best-corrected visual acuity tests
Time frame: 2 weeks
Primary pharmacokinetic endpoints will include: AUC(0-24), Cmax after repeat administration of pazopanib ophthalmic solution, Tmax, and trough steady-state plasma pazopanib concentration (Cτ)
Time frame: 2 weeks
1 secondary outcome
Secondary pharmacokinetic parameters include: area under the plasma drug concentration versus time curve [AUC(0-t)], observed accumulation ratio (Ro), and apparent terminal half-life (t1/2) after repeat administration will be analyzed
Time frame: 2 weeks
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 Nov 2017.
- Derived from this study: PubMed 24896137Singh R, Wurzelmann JI, Ye L, Henderson L, Hossain M, Trivedi T, Kelly DS. Clinical evaluation of pazopanib eye drops in healthy subjects and in subjects with neovascular age-related macular degeneration. Retina. 2014 Sep;34(9):1787-95. doi: 10.1097/IAE.0000000000000179.
- Results for study 113748 can be found on the GSK Clinical Study RegisterLink 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 pazopanib in people with Macular Degeneration, 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 8 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 14 Nov 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. Some participants in this study may receive a placebo. 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?
Clinical safety data from AE reporting, clinical observations, physical examinations, vital signs (blood pressure and heart rate), clinical laboratory tests including urinalysis, general ophthalmic examinations, and best-corrected visual acuity tests (time frame: 2 weeks). 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?
On the ClinicalTrials.gov record for NCT01072214, 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 Nov 2017.