SAFETY AND EFFICACY ASSESSMENTS

Transcription

1 SAFETY AND EFFICACY ASSESSMENTS The observations and procedures described in (Primary Arthritis Assessments) and the Hip or Knee Pain on motion assessment described in (Secondary Arthritis Assessment) are performed at the Week 3 and the Week 8 or Final Visit. Arthritis assessments are limited to the index joint selected at the baseline evaluation. 5.1 Primary Efficacy Assessments The following OA Assessments are considered the primary measures of efficacy: 1. Physician's OA Assessment of Arthritis; 2. Patient's OA Assessment of Arthritis; and 3. Hip or Knee Pain while Standing Physician s OA Assessment of Arthritis: The physician estimates the overall condition of the arthritis of the index joint at the time of the patient's visit. This assessment is based on the patient's disease signs and is quantified by using the scale in Table 1 under Appendix A Patient's OA Assessment of Arthritis: Subjects will answer the following question: As a person with osteoarthritis, consider how the symptoms and limitations affect your daily activities? The Patient s OA Assessment of Arthritis is graded using the scale in Table 1 under Appendix A Hip or Knee Pain while Standing: Pain while standing in the index joint (hip or knee) will be evaluated by asking the patient the following question and using the scale in Table 2 under Appendix A. In general, how much pain have you experienced in your hip or knee in the past 24 hours? OA Symptom Criteria All study subjects must be experiencing moderate to severe symptoms related to their OA at the time of study enrollment as defined below. 1. Physician's OA Assessment of Arthritis must be fair, poor or very poor 2. Patient's OA Assessment of Arthritis must be fair, poor or very poor 3. Hip or Knee Pain while Standing must be moderate, severe or very severe.

2 5.2 Secondary Efficacy Assessments The following are considered secondary objective measurements of efficacy: 1. Hip or Knee Pain during Motion; 2. OA Quality of Life Questionaires a. OA QoL Scale b. ADL Assessment 3. Treatment Failure Hip or Knee Pain during Motion Hip or Knee Pain during Motion is scored using the scale in Table 3 under Appendix A. The following method is to be used to assess hip joint pain on passive motion. With the patient in supine position and with the hip flexed at 90 degrees, the Investigator should grasp the patient's leg above the ankle and above the knee and perform internal and external rotation maneuvers within the available range of motion (or until the patient indicates movement causes pain). A judgment of pain on motion should be reached in a single rotation maneuver and repetitive maneuvers should not be done. Investigator should avoid forcing the hip into extreme rotation at the point of maximum rotation QUALITY OF LIFE (QOL) ASSESSMENTS A. OA QoL Scale The patient prior to any other procedures being performed should complete the OA QoL Scale. This is a self-administered questionnaire probing clinically important, patient-relevant outcomes in subjects with OA of the hip or knee. The patient is asked to respond to items regarding pain, stiffness and physical function. In addition, the patient is asked to identify items of importance, which he hopes will be favorably influenced by the subsequent intervention. These items represent the principal focus of the questionnaire. B. ADL Assessment The ADL Assessment is a generic QoL instrument, which has items covering activities of daily living. The ADL Assessment will query the patient for a sixweek recall at the baseline visit, two week recall at Week 3, and 4 week recall at Week 8 or the final visit. The patient should complete it before any other procedures are performed Treatment Failure (Lack of Efficacy) A treatment failure is any subject that: Chooses to stop the study participation due to their view of lack of improvement or worsening Osteoarthritis symptoms or antacid symptoms; The investigator s determination to terminate due to lack of improvement or worsening of the subject s Osteoarthritis symptoms and antacid symptoms; The subject uses exclusionary medications, refer to section Treatment Period Exclusionary, to treat either Osteoarthritis symptoms or antacid symptoms;

3 Subjects administering greater than 6 tablets per day for 3 consecutive days should be early terminated and considered lack of efficacy. 5.3 Safety Assessments The following are considered assessments of safety: 1. Gastroduodenal analysis; 2. Clinical laboratory analysis; 3. Adverse event assessment; 4. Changes in the physical exam UGI Endoscopy An upper gastrointestinal (UGI) endoscopic examination must be performed within seven days prior to the first dose of study medication and the findings recorded on the appropriate CRF. The same endoscopist, using the same equipment and measuring devices, should perform the baseline and all other endoscopies. The mucosa of the stomach and the duodenum will each be assigned a separate score using the scale shown in Table 4 under Appendix A Clinical Laboratory Tests and Other Specialized Procedures A. Blood Samples Blood samples will be obtained for the following clinical laboratory tests and the results reviewed by the Investigator within seven days prior to the first dose of study medication. A central laboratory will perform all tests. i. Hematology Hemoglobin, WBC, Hematocrit, Platelet count (estimate not acceptable) ii. Chemistry Creatinine, Total Bilirubin, AST (SGOT), ALT (SGPT), Alkaline Phosphatase iii. IV. Helicobacter pylori (H. pylori) All subjects will be screened at baseline for H. pylori antibodies using Flexure HP serological testing. Pregnancy Test If the patient is a female of childbearing potential, a serum pregnancy test will be performed, reviewed and confirmed as negative prior to receiving the first dose of study medication. B. CLO Test At the final visit, a CLO test will be performed to test for the presence of the H. pylori organism. The CLO tests are performed at the investigational site Adverse Events and Serious Adverse Events The term "adverse event" is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the

4 medicinal (investigational) product. It may also be an increase in severity of frequency of a disease or condition from the medical history or any clinically significant finding detected during physical examination. An unexpected adverse event is any adverse event that is not identified in nature, severity or frequency in the investigational brochure. Associated with the use of the drug means that there is a reasonable possibility that the event may have been caused by the drug. Severity is recorded as either, mild, moderate or severe according to the following definitions below: Mild Moderate Severe Causing no limitation of usual activities. Causing some limitation of usual activities. Causing inability to carry out usual activities. A "serious" adverse event is defined as any event that results in the following: Is fatal; Is life threatening, meaning, the subject was, in the view of the Investigator, at immediate risk of death from the reaction as it occurred, it does not include a reaction that, had it occurred in a more serious form, might have caused death; Is permanently disabling; Requires, or prolongs, inpatient hospitalization; Is a congenital anomaly; Important medical events that require medical or surgical intervention that in the judgment of the investigator prevented the outcome in the SAE definition. This can include abnormal labs Physical Exam Any change in the physical exam from baseline that the Investigator considers clinically significant or a worsening of a disease or condition is recorded as an adverse event. 6.0 VISITS AND PROCEDURES The pretreatment period consists of two contacts: screening and baseline. 6.1 Screening (-2 to - 34 Days) Obtain informed consent Medical history Assess concomitant medication usage, check exclusionary medication for possible washout periods and appropriate scheduling of the baseline visit refer to section and Laboratory refer to section A Schedule Endoscopy and Baseline visit During this contact subject's medical history will be screened against the inclusion/exclusion criteria. Subjects taking NSAIDs must discontinue these medications at this time. Subjects receiving no prior NSAIDs/analgesics for their OA can have the OA assessments, OA QoL, and physical exam performed

5 immediately. If they fulfill the symptom criteria defined under section OA Symptom Criteria and do not have any physical findings that exclude them from the study schedule the endoscopy and the baseline visit within two to four days from the screening visit. Those taking NSAIDs/analgesics will have to discontinue these medications at least 7 days prior to the baseline evaluation and will not be admitted to the study until their symptoms fulfill the criteria defined under section OA Symptom Criteria. Acetaminophen up to 3 gm/day may be taken during the NSAID washout period, only if absolutely necessary, but must be avoided within 24 hours prior to the baseline arthritis assessments. During this washout period an endoscopy is performed for evaluation at the baseline visit. Baseline (Day 1) The baseline visit requires the following procedures unless some were performed at the screening visit: Physical Examination with Vital Signs (Respiration Rate per minute, Blood Pressure, Heart Rate per minute, Height, Weight, Temperature). Arthritis Assessments Baseline OA assessments of the index joint include: a. Physician's OA assessment of arthritis b. Patient's OA assessment of arthritis c. Hip or knee pain while standing d. Hip or knee pain on motion Arthritis QoL Assessments (OA QoL Scale and ADL Assessment) Assess Concomitant Medications Assess the Laboratory, Hp Flexure and Endoscopy results Assess Inclusion and Exclusion criteria Discontinue Antacid Therapy Randomize and Dispense and Instruct Subject to Day 1 Study Medications Dispense Diary 6.2 Week 3 (Day 21) (+/-3days) Arthritis Assessments OA assessments of the index joint include: a. Physician's OA assessment of arthritis b. Patient's OA assessment of arthritis c. Hip or knee pain while standing d. Hip or knee pain on motion Arthritis QoL Assessments (OA QoL Scale and ADL Assessment)

6 Assess Concomitant Medications Laboratory Perform Study Drug Accountability Dispense Week 3 Study Medications and Diary Schedule Week 8 Schedule Endoscopy either two days before or the day of the Week 8 visit 6.3 Week 8 (Day 56) (+/-5 days) Arthritis Assessments OA assessments of the index joint include: a. Physician's OA assessment of arthritis b. Patient's OA assessment of arthritis c. Hip or knee pain while standing d. Hip or knee pain on motion Arthritis QoL Assessments (OA QoL Scale and ADL Assessment) Physical Exam with Vital Signs (Respiration Rate per minute, Blood Pressure, Heart Rate per minute, Height, Weight, Temperature). Assess Concomitant Medications Laboratory Perform Study Drug Accountability Assess Endoscopy results CLO test Prescribe routine OA and Ulcer protection medications Dispense Diary Schedule Week 11 visit 6.4 Week 11 (Day 77) (+/- 5 days) Physical Exam* with vital signs (Respiration Rate per minute, Blood Pressure, Heart Rate per minute, Height, Weight, Temperature). Assess Concomitant Medications Laboratory* Endoscopy* *Only performed if a clinical significant finding present at Week 8

7 Procedures Obtain Consent Medical History Assess Inclusion /Exclusion Criteria NSAIDs Discontinued SCHEDULE OF OBSERVATIONS AND PROCEDURES Pre-Treatment Screening (Day 2 to 34) Pre-Treatment Baseline (Day 1) Treatment Week 3 Days 21 Treatment Week 8 Days 56 Follow Up Week 11 Days 77 Routine antacid therapy discontinued Physical Exam with Vital Signs * Arthritis Assessments Physician s OA Assessment Patient s OA Assessment Hip and Knee pain while standing Hip and Knee pain during motion OA Quality of Life Scale ADL Assessment UGI Endoscopy Laboratory Tests Hp Flexure CLO Test * * Assess Concomitant Medications Assess Adverse Events Dispense Study Medications Dispense Diary Tablet Counts *Only if perform at Week 11 abnormal from Week 8