A Safety Study to Evaluate Pazopanib Eye Drops in Healthy Volunteers

NCT01072214 | Completed Phase 1

• 1 other identifier: 113748
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Macular Degeneration

Keywords

Pazopanib; Tolerability; Pharmacokinetics; GW786034; Safety

Outcome Measures

Primary Outcomes (2)

• 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

  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)

  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

  2 weeks

Study Arms (4)

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

Drug: pazopanib

TBD COHORT 2

EXPERIMENTAL

Dose escalation amount to be determined (TBD) after results from Cohort 1 analyzed

Drug: pazopanib

Placebo

PLACEBO COMPARATOR

Subjects will receive placebo (drops without drug).

Drug: Placebo

TBD COHORT 3

EXPERIMENTAL

Dose escalation amount to be determined (TBD) after results from Cohort 2 analyzed

Drug: pazopanib

Interventions

pazopanib DRUG

gw786034

TBD COHORT 2

Placebo DRUG

placebo

Placebo

Eligibility Criteria

• Age: 20 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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:

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Glendale, California, 91206, United States

Location

Related Publications (1)

• 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.

  PMID: 24896137 DERIVED

Related Links

• Results for study 113748 can be found on the GSK Clinical Study Register

MeSH Terms

Conditions

Macular Degeneration

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2010
• First Posted: February 22, 2010
• Study Start: March 9, 2010
• Primary Completion: June 28, 2010
• Study Completion: June 28, 2010
• Last Updated: November 14, 2017

Record last verified: 2017-11

Locations

US (1)