A Study to Characterize Diclofenac's Plasma and Knee Exposure After Application of Diclofenac Gel to the Knee of Subjects With Osteoarthritis That Have a Scheduled Arthroplasty

Inclusion Criteria: * Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study before any assessment is performed. * Male and female participants who, at the time of screening, are ≥ 50 years of age. * Participant has a diagnosis of OA of the knee requiring arthroplasty and is scheduled for single knee arthroplasty, with radiographic evidence within last 6 months confirming Kellgren Lawrence grade of 2 or more. * Participant is in general good physical health and deemed fit for surgery, as judged by the investigator and no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, respiratory rate and temperature measurement, 12 lead ECG or clinical laboratory tests. * Body Mass Index (BMI) of 17.5 to less than 40 kg/m2; and a total body weight \>50 kg (110 lbs). * Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. * Female participants of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for at least 21 days after the last dose of assigned treatment. Female participants who are not of childbearing potential must meet following requirements: Female participants who are of childbearing potential and are sexually active and at risk for pregnancy must agree to use a highly effective method of contraception consistently and correctly for the duration of the active study period (onwards from screening) and for at least 21 days after the last dose of investigational product. The investigator or his or her designee, in consultation with the participant, will confirm that the participant has selected an appropriate method of contraception for the individual participant from the permitted list of contraception methods (see below) and instruct the participant in its consistent and correct use. Participants need to affirm that they meet the criteria for the correct use of at least 1 of the selected methods of contraception. The investigator or his or her designee will discuss with the participant the need to use highly effective contraception consistently and correctly according to the schedule of activities and document such conversation in the participant's chart. In addition, the investigator or his or her designee will instruct the participant to call immediately if the selected contraception method is discontinued or if pregnancy is known or suspected in the participant. Highly effective methods of contraception are those that, alone or in combination, result in a failure rate of less than 1% per year when used consistently and correctly (i.e., perfect use) and include the following a)Established use of oral, inserted, injected, transdermal, or implanted hormonal methods of contraception is allowed provided the participant plans to remain on the same treatment throughout the entire study and has been using that hormonal contraceptive for an adequate period of time to ensure effectiveness as deemed appropriate by the investigator, b) Correctly placed copper-containing intrauterine device (IUD), c) Male condom or female condom used with a spermicide (i.e., foam, gel, film, cream, or suppository), d) Male sterilization with absence of sperm in the post-vasectomy ejaculate e) Bilateral tubal ligation / bilateral salpingectomy or bilateral tubal occlusive procedure (provided that occlusion has been confirmed in accordance with the device's label), f)Female who meets the criteria for non-childbearing potential as described below. Female participants of non-childbearing potential must meet at least one of the following criteria: 1) Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state, 2) Have undergone a documented hysterectomy and/or bilateral oophorectomy, 3) Have medically confirmed ovarian failure. All other female participants (including females with tubal ligations) will be considered to be of childbearing potential. Exclusion Criteria: * Participants who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are GSK employees directly involved in the conduct of the study. * Participation in other studies involving investigational drug(s) within one month prior to study entry and/or during study participation. * Acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. * Pregnant female participants. * Breastfeeding female participants. * Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. * Participants in whom attacks of asthma, angioedema, urticaria, or acute rhinitis are precipitated by acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs). * Participants whose skin around the knee is broken, diseased or has skin wounds or open injuries. * Unwilling or unable to comply with the following lifestyle guidelines described in the protocol or investigator instructions: a) Meals and Dietary Restrictions: No specific meal or dietary restriction is required for the study. Participants will follow the perioperative guidance with respect to meals and dietary restrictions as provided by the surgical center. Participants must abstain from all food and drink (except water) at least 4 hours prior to any safety laboratory evaluations, b)Alcohol, Caffeine and Tobacco: participants will follow the perioperative guidance with respect to alcohol and caffeine intake and use of tobacco- or nicotine containing products as provided by the surgical center, c) Activity: participants will follow the perioperative guidance with respect to activity as provided by the surgical center, d) Contraception: Female participants who are of childbearing potential and are sexually active and at risk for pregnancy must agree to use a highly effective method of contraception consistently and correctly for the duration of the active study period (onwards from screening) and for at least 21 days after the last dose of investigational product. The investigator or his or her designee, in consultation with the participant, will confirm that the participant has selected an appropriate method of contraception for the individual participant from the permitted list of contraception methods (see below) and instruct the participant in its consistent and correct use. Participants need to affirm that they meet the criteria for the correct use of at least 1 of the selected methods of contraception. The investigator or his or her designee will discuss with the participant the need to use highly effective contraception consistently and correctly according to the schedule of activities and document such conversation in the participant's chart. In addition, the investigator or his or her designee will instruct the participant to call immediately if the selected contraception method is discontinued or if pregnancy is known or suspected in the participant. Highly effective methods of contraception are those that, alone or in combination, result in a failure rate of less than 1% per year when used consistently and correctly (i.e., perfect use) and include the following: 1) Established use of oral, inserted, injected, transdermal, or implanted hormonal methods of contraception is allowed provided the participant plans to remain on the same treatment throughout the entire study and has been using that hormonal contraceptive for an adequate period of time to ensure effectiveness as deemed appropriate by the investigator, 2) Correctly placed copper-containing intrauterine device (IUD), 3) Male condom or female condom used with a spermicide (i.e., foam, gel, film, cream, or suppository), 4) Male sterilization with absence of sperm in the post-vasectomy ejaculate, 5) Bilateral tubal ligation / bilateral salpingectomy or bilateral tubal occlusive procedure (provided that occlusion has been confirmed in accordance with the device's label), 6)Female who meets the criteria for non-childbearing potential as described below. Female participants of non-childbearing potential must meet at least one of the following criteria: a) Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state, b) Have undergone a documented hysterectomy and/or bilateral oophorectomy, c) Have medically confirmed ovarian failure. All other female participants (including females with tubal ligations) will be considered to be of childbearing potential e) Screen Failures: Screen failures are defined as participants who consent to participate in the clinical study but are not subsequently randomized. In order to ensure transparent reporting of screen failure participants, a minimal set of screen failure information will include screening number, date of screening, demography (gender, year of birth, age), screen failure details (e.g., withdrawal of consent), eligibility criteria, and any serious adverse events. Screening failures will be replaced in the recruitment schedule until the required number of participants are randomized. Individuals who do not meet the criteria for participation in this study (screen failure) may not be re-screened, f) Sponsor's Qualified Medical Personnel: The contact information for the sponsor's appropriately qualified medical personnel for the study is documented in the study contact list located in the supporting study documentation. The contact number can be used by investigational staff if they are seeking advice on medical questions or problems; however, it should be used only in the event that the established communication pathways between the investigational site and the study team are not available. It is therefore intended to augment, but not replace, the established communication pathways between the investigational site and the study team for advice on medical questions or problems that may arise during the study. The contact number is not intended for use by the participant directly, and if a participant calls that number, he or she will be directed back to the investigational site. To facilitate access to appropriately qualified medical personnel on study-related medical questions or problems, participants are provided with a contact card. The contact card contains, at a minimum, protocol identifiers, participant study numbers, contact information for the investigational site, and contact details in the event that the investigational site staff cannot be reached to provide advice on a medical question or problem identified from the participant's healthcare professional other than the investigator. * Use of prescription or nonprescription drugs (unless deemed necessary by investigator), NSAIDs, COX-2 inhibitors and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study treatment and during the study. Specifically if, during the washout period or the treatment period, the participant is unwilling to avoid the use of any topical or systemic analgesic or anti-inflammatory treatments other than the study medication, the rescue medication, and if needed codeine or tramadol. * Use of one or more of the following treatments prior to the screening visit or between screening and baseline visit: a) any topical NSAID treatment between screening and baseline visit, b) any intra-articular or peri-articular procedures or injections in either knee within the previous 3 months, c) any systemic treatment with corticosteroids within the previous 6 weeks (topical treatments with corticosteroids not related to either knee are permitted up to screening visit), d) any chondroprotectant or disease-modifying OA drugs, such as glucosamine or chondroitin sulfate, unless dose was stable over the previous month and will be maintained throughout the study, e) any systemic anti-inflammatory or analgesic drugs at screening if 5 times their elimination halftime exceeds 7 days (i.e., if half-life \> 33.6 hrs), f) anticoagulants such as warfarin or heparin in the preceding week or antiaggregants within the previous month other than aspirin at stable low doses started at least one month before randomization and kept at a constant dose throughout the study or anticoagulant therapy for surgery, g) any other investigational drugs within the previous month or 5 half lives preceding the first dose of investigational product (whichever is longer). * A positive urine drug screen during Screening (Day -7). * Any condition possibly affecting drug absorption (e.g., gastrectomy). * History of regular alcohol consumption exceeding 14 drinks/week (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening. * Participants who have previously been enrolled in this study.