Long-Term Study of the Effects of Navarixin (SCH 527123, MK-7123) in Participants With Moderate to Severe COPD (MK-7123-019)

December 10, 2018 updated by: Merck Sharp & Dohme LLC

A 2-Year, Dose Range-Finding, Adaptive-Design Study of the Effects of SCH 527123 in Subjects With Moderate to Severe COPD

Neutrophils are thought to play an important role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Navarixin (SCH 527123, MK-7123) is an antagonist of the cysteine-X-cysteine chemokine receptor 2 (CXCR2) and is thought to reduce neutrophil migration to the diseased lung. It is theorized that reducing neutrophil migration to the diseased lung will improve a participant's symptoms and the natural history of the disease.

The study will consist of a 2-week screening period followed by a 2-year (104-week) double-blind treatment period. The 2-year Treatment Period will be made up of two phases: a 26-week (6-month) dose range-finding phase with 3 active arms and 1 placebo arm (Period 1), followed by a 78-week (18-month) long-term safety and efficacy phase (Period 2). Participants participating in the original 6-month study (Period 1) may elect not to continue into the 18-month extension study (Period 2).

Hypothesis: navarixin, 50 mg, or the highest remaining dose if the 50-mg dose is discontinued, is superior to placebo with respect to improving airflow.

Study Overview

Status

Terminated

Conditions

Study Type

Interventional

Enrollment (Actual)

616

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

41 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of COPD for at least 2 years based on American Thoracic Society/European Respiratory Society (ATS/ERS) current guidelines or symptoms consistent with COPD for at least 2 years.
  • >40 to <=75 years of age, of either sex, and of any race.
  • No exacerbation or respiratory infection in the past 6 weeks.
  • Smoker or ex-smoker with more than 10 pack-year history.

Exclusion Criteria:

  • Diagnosis of asthma or other clinically relevant lung disease (other than COPD), i.e., sarcoidosis, tuberculosis, pulmonary fibrosis, severe bronchiectasis, or lung cancer.
  • Significant X-ray findings.
  • Use of supplemental oxygen for >12 hours/day.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Navarixin 10 mg
Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally once daily (QD) for up to 2 years
Navarixin 10 mg and 30 mg capsules
Placebo to navarixin capsules
Short-acting β-agonist (SABA), anticholinergic, or a combination SABA/anticholinergic
Experimental: Navarixin 30 mg
Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years
Navarixin 10 mg and 30 mg capsules
Placebo to navarixin capsules
Short-acting β-agonist (SABA), anticholinergic, or a combination SABA/anticholinergic
Experimental: Navarixin 50 mg
Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years
Navarixin 10 mg and 30 mg capsules
Short-acting β-agonist (SABA), anticholinergic, or a combination SABA/anticholinergic
Placebo Comparator: Placebo
Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Placebo to navarixin capsules
Short-acting β-agonist (SABA), anticholinergic, or a combination SABA/anticholinergic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (Period 1)
Time Frame: Baseline and Week 26
FEV1, as measured in liters by spirometry, is the amount of air expired in 1 second. Participants were assessed for post-bronchodilator FEV1 30 minutes after bronchodilator administration (4 puffs of albuterol/salbutamol or equivalent separated by 30-second intervals) (reversibility test) at Baseline and Week 26.
Baseline and Week 26
Percentage of Participants With an Adverse Event (AE) Related to a Blood Absolute Neutrophil Count (ANC) of Less Than 1.5x10^9 Cells/L
Time Frame: Up to 104 weeks
The percentage of participants who experienced an AE related to an ANC of less than 1.5x10^9 cells/L at one or more visits during the first 26 weeks, the first 52 weeks and the first 104 weeks was to be calculated.
Up to 104 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Post-bronchodilator FEV1 (Period 2)
Time Frame: Baseline and Week 52, Week 104
FEV1, as measured in liters by spirometry, is the amount of air expired in 1 second. Participants were to be assessed for post-bronchodilator FEV1 30 minutes after bronchodilator administration (4 puffs of albuterol/salbutamol or equivalent separated by 30-second intervals) (reversibility test) at Baseline, Week 52 and Week 104.
Baseline and Week 52, Week 104
Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Time Frame: Up to 26 , 52 and 104 weeks
COPD exacerbation is defined as any deterioration of symptoms that leads to an increase in bronchodilator use on 2 or more consecutive days, or administration (at investigator's discretion) of antibiotics and/or systemic corticosteroids (above participant's usual dose), or an unscheduled COPD-related doctor visit, hospitalization or emergency room treatment. The numbers of participants who experienced at least one moderate to severe COPD exacerbation during the first 26 weeks, the first 52 weeks and the first 104 weeks of treatment were to be summarized.
Up to 26 , 52 and 104 weeks
Percentage of Participants With a Moderate to Severe COPD Exacerbation
Time Frame: Up to 26, 52 and 104 weeks
COPD exacerbation is defined as any deterioration of symptoms that leads to an increase in bronchodilator use on 2 or more consecutive days, or administration (at investigator's discretion) of antibiotics and/or systemic corticosteroids (above participant's usual dose), or an unscheduled COPD-related doctor visit, hospitalization or emergency room treatment. The percentages of participants who experienced at least one moderate to severe COPD exacerbation during the first 26 weeks, the first 52 weeks and the first 104 weeks of treatment were to be summarized.
Up to 26, 52 and 104 weeks
Total Exacerbations of Chronic Pulmonary Disease Tool-Patient-Recorded Outcome (EXACT-PRO) Questionnaire Score
Time Frame: At 26, 52 and 104 weeks
The total score on the EXACT-PRO questionnaire is used to determine the frequency, severity, and duration of exacerbations of COPD. The 14-item EXACT-PRO questionnaire was to be completed by participants every evening to describe their experience of COPD during that day. Assessments were included for Breathlessness (5 items), Cough and Sputum (2 items), Chest Symptoms (3 items), and 4 additional items (Difficulty with Sputum, Tired or Weak, Sleep Disturbance, and Psychological State). Each item was measured on a 5- or 6-point scale. The total EXACT-PRO questionnaire score could range from 0 to 100, with a higher score indicating a more severe health state.
At 26, 52 and 104 weeks
Induced Sputum Absolute Neutrophil Counts
Time Frame: Baseline, Week 26, Week 52, Week 104
Induced sputum samples were to be obtained from participants via the nebulized method for analysis of absolute neutrophil counts at Week 26, Week 52 and Week 104. The reported Baseline least squares (LS) means and standard deviations (SDs) are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an analysis of variance (ANOVA) method using pooled SD values is the assumption that the SDs are similar across treatment groups.
Baseline, Week 26, Week 52, Week 104
Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score
Time Frame: Baseline and Week 26, Week 52, Week 104
The SGRQ-C consists of 40 items aggregated into 3 component scores: Symptoms (frequency/severity), Activity (limited by breathlessness), Impacts (social functioning, psychological disturbances), and a Total score. Each response to a question is assigned a weight. Component scores are calculated by summing the weights from all positive items in that component, dividing by the sum of weights for all items in that component, and multiplying this number by 100. Component scores could range from 0-100, with a higher component score indicating greater disease burden. The Total score is calculated by summing the weights to all the positive responses in each component, dividing by the sum of weights for all items in the questionnaire, and multiplying this number by 100. SGRQ-C Total scores could range from 0-100, with a higher SGRQ-C Total score indicating greater disease burden. Participants were to assess their COPD symptoms, activity and impact at Baseline, Week 26, Week 52, and Week 104.
Baseline and Week 26, Week 52, Week 104
Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)
Time Frame: Baseline and Week 26, Week 52, Week 104
The 6-minute walk test measures the distance participants can walk quickly on a flat, hard surface in 6 minutes. The 6-minute walk test was to be conducted at Baseline, Week 26, Week 52 and Week 104.
Baseline and Week 26, Week 52, Week 104
Change From Baseline in Pre-bronchodilator FEV1
Time Frame: Baseline and Week 26, Week 52, Week 104
FEV1, as measured in liters by spirometry, is the amount of air expired in 1 second. Pre-bronchodilator FEV1 was to be assessed immediately before bronchodilator administration at Baseline, Week 26, Week 52 and Week 104.
Baseline and Week 26, Week 52, Week 104
Change From Baseline in Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity (FEF25%-75%) Test
Time Frame: Baseline and Week 26, Week 52, Week 104
Mid-Breath Forced Expiratory Flow (FEF25%-75%), as measured in liters/minute by spirometry, is the rate at which participants breathe out air from 25 percent of their breath to 75 percent of their breath. FEF25%-75% was to be assessed at Baseline, Week 26, Week 52 and Week 104.
Baseline and Week 26, Week 52, Week 104
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)
Time Frame: Baseline and Week 26, Week 52, Week 104
FVC, as measured in liters by spirometry, is the amount of air forcibly exhaled from the lungs after taking the deepest breath possible. Post-bronchodilator FVC was to be assessed 30 minutes after bronchodilator administration (4 puffs of albuterol/salbutamol or equivalent separated by 30-second intervals) at Baseline, Week 26, Week 52 and Week 104.
Baseline and Week 26, Week 52, Week 104
Change From Baseline in Functional Residual Capacity (FRC)
Time Frame: Baseline and Week 26, Week 52, Week 104
FRC, as measured in liters by body plethysmography, is the volume of air present in the lungs at the end of passive expiration. FRC was to be assessed after post-bronchodilator spirometry tests were performed at Baseline, Week 26, Week 52 and Week 104.
Baseline and Week 26, Week 52, Week 104
Change From Baseline in Total Lung Capacity (TLC)
Time Frame: Baseline and Week 26, Week 52, Week 104
TLC, as measured in liters by body plethysmography, is the most amount of air lungs can hold at the top of breathing in. TLC was to be assessed after post-bronchodilator spirometry tests were performed at Baseline, Week 26, Week 52 and Week 104.
Baseline and Week 26, Week 52, Week 104
Change From Baseline in Inspiratory Capacity (IC)
Time Frame: Baseline and Week 26, Week 52, Week 104
IC, as measured in liters by body plethysmography, is the maximum amount of air inspired when taking a slow, full inspiration with no hesitation from a position of passive end-tidal expiration (i.e. FRC) to a position of maximal inspiration. IC was to be assessed after post-bronchodilator spirometry tests were performed at Baseline, Week 26, Week 52 and Week 104.
Baseline and Week 26, Week 52, Week 104
Change From Baseline in Morning Peak Expiratory Flow (PEF)
Time Frame: Baseline and Week 26, Week 52, Week 104
PEF, as measured in liters/minute with a peak flow meter, is the maximum speed of expiration. Participants were to perform at least 3 and up to 5 PEF measurements in the morning before taking study drug. PEF was to be assessed at Baseline, Week 26, Week 52 and Week 104.
Baseline and Week 26, Week 52, Week 104
Change From Baseline in Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Index Score
Time Frame: Baseline and Week 26, Week 52, Week 104
The BODE index is a composite score assessing COPD prognosis that consists of 4 variables that are individually scored: FEV1 percent predicted, 6-Minute Walk Test, Modified Medical Research Council (MMRC) dyspnea scale and body mass index (BMI). The FEV1 percent predicted was scored from ≥65% (0 points, less airway obstruction) to ≤35% (3 points, greater airway obstruction). The 6-Minute Walk Distance was scored from: ≥350 meters (0 points, good exercise capacity) to ≤149 meters (3 points, poor exercise capacity). The MMRC Dyspnea Scale was scored from: MMRC 0: Dyspneic on strenuous exercise (0 points) to MMRC 4: Cannot leave house; breathless on dressing/undressing (3 points). BMI was scored as: >21 (0 points) and ≤21 (1 point). Variable scores were summed to produce a BODE index score. BODE index scores could range from 0 to 10, with a higher score correlating with an increased risk of COPD mortality. BODE index scores were to be assessed at Baseline, Week 26, Week 52 and Week 104.
Baseline and Week 26, Week 52, Week 104
Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score
Time Frame: Baseline and Week 26, Week 52, Week 104
The MMRC dyspnea scale is used to assess participant breathlessness. The MMRC dyspnea scale consists of five grades that describe almost the entire range of respiratory disability from none (Grade 0=Not troubled with breathlessness except with strenuous exercise) to almost complete incapacity (Grade 4=Too breathless to leave the house or breathless when dressing or undressing). MMRC dyspnea scores were to be assessed at Baseline, Week 26, Week 52 and Week 104.
Baseline and Week 26, Week 52, Week 104
Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)
Time Frame: Baseline, Week 26, Week 52, Week 104
Induced sputum samples were to be collected from participants via the nebulized method prior to study drug administration at Week 26, Week 52 and Week 104. IL-8 levels were measured by enzyme-linked immunosorbent assay (ELISA) in the sputum supernatant. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.
Baseline, Week 26, Week 52, Week 104
Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)
Time Frame: Baseline, Week 26, Week 52, Week 104
Induced sputum samples were to be collected from participants via the nebulized method prior to study drug administration at Week 26, Week 52 and Week 104. MPO levels were measured by ELISA in the sputum supernatant. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.
Baseline, Week 26, Week 52, Week 104
Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase
Time Frame: Baseline, Week 26, Week 52, Week 104
Induced sputum samples were to be collected from participants via the nebulized method prior to study drug administration at Week 26, Week 52 and Week 104. Neutrophil elastase levels were measured in the sputum supernatant. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.
Baseline, Week 26, Week 52, Week 104
Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)
Time Frame: Baseline, Week 26, Week 52, Week 104
Induced sputum samples were to be collected from participants via the nebulized method prior to study drug administration at Week 26, Week 52 and Week 104. MMP-9 levels were measured by ELISA in the sputum supernatant. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.
Baseline, Week 26, Week 52, Week 104
Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)
Time Frame: Baseline, Week 26, Week 52, Week 104
Blood samples were to be collected prior to study drug administration to determine participant plasma hs-CRP levels at Week 26, Week 52 and Week 104. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.
Baseline, Week 26, Week 52, Week 104
Plasma Inflammatory Biomarker Levels: Fibrinogen
Time Frame: Baseline, Week 26, Week 52, Week 104
Blood samples were to be collected prior to study drug administration to determine participant plasma fibrinogen levels at Week 26, Week 52 and Week 104. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.
Baseline, Week 26, Week 52, Week 104
Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)
Time Frame: Baseline, Week 26, Week 52, Week 104
Blood samples were to be collected prior to study drug administration to determine participant plasma MPO levels at Week 26, Week 52 and Week 104. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.
Baseline, Week 26, Week 52, Week 104
Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)
Time Frame: Baseline, Week 26, Week 52, Week 104
Blood samples were to be collected prior to study drug administration to determine participant plasma MMP-9 levels at Week 26, Week 52 and Week 104. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.
Baseline, Week 26, Week 52, Week 104
Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase
Time Frame: Baseline, Week 26, Week 52, Week 104
Blood samples were to be collected prior to study drug administration to determine participant plasma neutrophil elastase levels at Week 26, Week 52 and Week 104. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.
Baseline, Week 26, Week 52, Week 104
Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)
Time Frame: Baseline, Week 26, Week 52, Week 104
Blood samples were to be collected prior to study drug administration to determine participant plasma ENA-78 levels at Week 26, Week 52 and Week 104. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.
Baseline, Week 26, Week 52, Week 104
Change From Baseline in Pre- and Post-6-Minute-Walk-Test Borg Scale Score
Time Frame: Baseline and Week 26, Week 52, Week 104
The 6-minute walk test measured the distance participants could walk quickly on a flat, hard surface in 6 minutes. The Borg scale is a method use to rate perceived exertion (0=Nothing at all [no exertion] to 10=Maximal [exertion]). Borg scale scores were to be assessed pre- and post-walk-test at Baseline, Week 26, Week 52 and Week 104. A higher score indicates greater perceived exertion.
Baseline and Week 26, Week 52, Week 104
Change From Baseline in Percent of Arterial Oxygen Saturation Measured by Pulse Oximetry Before and After the 6-Minute Walk Test
Time Frame: Baseline and Week 26, Week 52, Week 104
The 6-minute walk test measured the distance participants could walk quickly on a flat, hard surface in 6 minutes. Percent (%) of arterial oxygen saturation, as measured by pulse oximetry, was to be assessed before and after the 6-minute walk test at Baseline, Week 26, Week 52 and Week 104.
Baseline and Week 26, Week 52, Week 104
Percentage of Participants Who Experienced an AE Related to Respiratory Infection
Time Frame: Up to 26 , 52 and 104 weeks
The percentage of participants who experienced an AE related to a respiratory infection or infestation, was to be calculated for the first 26 weeks, the first 52 weeks and the first 104 weeks of treatment.
Up to 26 , 52 and 104 weeks
Percentage of Participants Who Experienced an AE Related to Any Type of Infection
Time Frame: Up to 26 , 52 and 104 weeks
The percentage of participants who experienced an AE related to any type of infection or infestation, was to be calculated for the first 26 weeks, the first 52 weeks and the first 104 weeks of treatment.
Up to 26 , 52 and 104 weeks

Collaborators and Investigators

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Publications and helpful links

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Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2009

Primary Completion (Actual)

March 1, 2011

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

October 1, 2009

First Submitted That Met QC Criteria

November 2, 2009

First Posted (Estimate)

November 3, 2009

Study Record Updates

Last Update Posted (Actual)

January 2, 2019

Last Update Submitted That Met QC Criteria

December 10, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Other Study ID Numbers

  • P05575 (Other Identifier: Merck Research Laboratories)
  • 2008-003780-38 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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