Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease
OBJECTIVE:To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy. METHODS:This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in...
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| Veröffentlicht in: | Neurology 2017-06, Vol.88 (23), p.2198-2206 |
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| container_title | Neurology |
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| creator | Stocchi, Fabrizio Rascol, Olivier Hauser, Robert A Huyck, Susan Tzontcheva, Anjela Capece, Rachel Ho, Tony W Sklar, Peter Lines, Christopher Michelson, David Hewitt, David J |
| description | OBJECTIVE:To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy.
METHODS:This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for |
| doi_str_mv | 10.1212/WNL.0000000000004003 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1212_WNL_0000000000004003</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>28490648</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3693-540902899eb3859a26ef0829a2a1a7929f462218257772722687be5dc6094cdb3</originalsourceid><addsrcrecordid>eNp9kF9LwzAUxYMobk6_gUg-wDrTtE2TRxn-g6Eiir6V2_bWxrVpSTLH_PRWpiI-eF_uhXvO4fAj5Dhks5CH_PTpZjFjvyZmLNoh4zDhIhARf94lY8a4DCKZyhE5cO6VseGZqn0y4jJWTMRyTLJ7MGXX6ncsqbcaGtpVtLfYQIkGjJ_SF_2GhoKjbWc6X6OFfjOl2tAevEbjHV1rX1ME22zoHdilNq4ztNQOweEh2augcXj0tSfk8eL8YX4VLG4vr-dni6CIhIqCJGZqKKsU5pFMFHCBFZN8OCCEVHFVxYLzUPIkTVOeci5kmmNSFoKpuCjzaELibW5hO-csVllvdQt2k4Us--SVDbyyv7wG28nW1q_yFssf0zegQSC3gnXXeLRu2azWaLMaofH1_9kfXzN2ug</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><source>Alma/SFX Local Collection</source><creator>Stocchi, Fabrizio ; Rascol, Olivier ; Hauser, Robert A ; Huyck, Susan ; Tzontcheva, Anjela ; Capece, Rachel ; Ho, Tony W ; Sklar, Peter ; Lines, Christopher ; Michelson, David ; Hewitt, David J</creator><creatorcontrib>Stocchi, Fabrizio ; Rascol, Olivier ; Hauser, Robert A ; Huyck, Susan ; Tzontcheva, Anjela ; Capece, Rachel ; Ho, Tony W ; Sklar, Peter ; Lines, Christopher ; Michelson, David ; Hewitt, David J ; Preladenant Early Parkinson Disease Study Group</creatorcontrib><description>OBJECTIVE:To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy.
METHODS:This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for <5 years who were not yet receiving L-dopa or dopamine agonists. Patients with a Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 (motor function) score ≥10 and Hoehn & Yahr score ≤3 were randomized 1:1:1:1:1 to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once daily, or placebo. The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS2+3).
RESULTS:The number of patients treated was 1,007. Neither preladenant nor rasagiline was superior to placebo after 26 weeks. The differences vs placebo (95% confidence interval) in UPDRS2+3 scores (with a negative difference indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30), preladenant 5 mg = 1.30 (−0.41, 2.94), preladenant 10 mg = 0.40 (−1.29, 2.11), and rasagiline 1 mg = 0.30 (−1.35, 2.03). Post hoc analyses did not identify a single causal factor that could explain the finding of a failed trial. Preladenant was generally well-tolerated with few patients discontinuing due to adverse events (preladenant 7%, rasagiline 3%, placebo 4%).
CONCLUSIONS:No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial. The lack of efficacy of the active control rasagiline makes it difficult to interpret the results.
CLINICAL TRIAL REGISTRATION:Clinicaltrials.govNCT01155479.
CLASSIFICATION OF EVIDENCE:This study provides Class I evidence that for patients with early PD, preladenant is not effective as monotherapy at the doses studied (2, 5, 10 mg).</description><identifier>ISSN: 0028-3878</identifier><identifier>EISSN: 1526-632X</identifier><identifier>DOI: 10.1212/WNL.0000000000004003</identifier><identifier>PMID: 28490648</identifier><language>eng</language><publisher>United States: American Academy of Neurology</publisher><subject>Activities of Daily Living ; Adenosine A2 Receptor Antagonists - therapeutic use ; Antiparkinson Agents - adverse effects ; Antiparkinson Agents - therapeutic use ; Dose-Response Relationship, Drug ; Double-Blind Method ; Female ; Humans ; Indans - adverse effects ; Indans - therapeutic use ; Internationality ; Male ; Middle Aged ; Motor Activity - drug effects ; Parkinson Disease - drug therapy ; Pyrimidines - adverse effects ; Pyrimidines - therapeutic use ; Severity of Illness Index ; Treatment Failure ; Triazoles - adverse effects ; Triazoles - therapeutic use</subject><ispartof>Neurology, 2017-06, Vol.88 (23), p.2198-2206</ispartof><rights>2017 American Academy of Neurology</rights><rights>2017 American Academy of Neurology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3693-540902899eb3859a26ef0829a2a1a7929f462218257772722687be5dc6094cdb3</citedby><cites>FETCH-LOGICAL-c3693-540902899eb3859a26ef0829a2a1a7929f462218257772722687be5dc6094cdb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28490648$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stocchi, Fabrizio</creatorcontrib><creatorcontrib>Rascol, Olivier</creatorcontrib><creatorcontrib>Hauser, Robert A</creatorcontrib><creatorcontrib>Huyck, Susan</creatorcontrib><creatorcontrib>Tzontcheva, Anjela</creatorcontrib><creatorcontrib>Capece, Rachel</creatorcontrib><creatorcontrib>Ho, Tony W</creatorcontrib><creatorcontrib>Sklar, Peter</creatorcontrib><creatorcontrib>Lines, Christopher</creatorcontrib><creatorcontrib>Michelson, David</creatorcontrib><creatorcontrib>Hewitt, David J</creatorcontrib><creatorcontrib>Preladenant Early Parkinson Disease Study Group</creatorcontrib><title>Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease</title><title>Neurology</title><addtitle>Neurology</addtitle><description>OBJECTIVE:To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy.
METHODS:This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for <5 years who were not yet receiving L-dopa or dopamine agonists. Patients with a Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 (motor function) score ≥10 and Hoehn & Yahr score ≤3 were randomized 1:1:1:1:1 to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once daily, or placebo. The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS2+3).
RESULTS:The number of patients treated was 1,007. Neither preladenant nor rasagiline was superior to placebo after 26 weeks. The differences vs placebo (95% confidence interval) in UPDRS2+3 scores (with a negative difference indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30), preladenant 5 mg = 1.30 (−0.41, 2.94), preladenant 10 mg = 0.40 (−1.29, 2.11), and rasagiline 1 mg = 0.30 (−1.35, 2.03). Post hoc analyses did not identify a single causal factor that could explain the finding of a failed trial. Preladenant was generally well-tolerated with few patients discontinuing due to adverse events (preladenant 7%, rasagiline 3%, placebo 4%).
CONCLUSIONS:No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial. The lack of efficacy of the active control rasagiline makes it difficult to interpret the results.
CLINICAL TRIAL REGISTRATION:Clinicaltrials.govNCT01155479.
CLASSIFICATION OF EVIDENCE:This study provides Class I evidence that for patients with early PD, preladenant is not effective as monotherapy at the doses studied (2, 5, 10 mg).</description><subject>Activities of Daily Living</subject><subject>Adenosine A2 Receptor Antagonists - therapeutic use</subject><subject>Antiparkinson Agents - adverse effects</subject><subject>Antiparkinson Agents - therapeutic use</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Humans</subject><subject>Indans - adverse effects</subject><subject>Indans - therapeutic use</subject><subject>Internationality</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Motor Activity - drug effects</subject><subject>Parkinson Disease - drug therapy</subject><subject>Pyrimidines - adverse effects</subject><subject>Pyrimidines - therapeutic use</subject><subject>Severity of Illness Index</subject><subject>Treatment Failure</subject><subject>Triazoles - adverse effects</subject><subject>Triazoles - therapeutic use</subject><issn>0028-3878</issn><issn>1526-632X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kF9LwzAUxYMobk6_gUg-wDrTtE2TRxn-g6Eiir6V2_bWxrVpSTLH_PRWpiI-eF_uhXvO4fAj5Dhks5CH_PTpZjFjvyZmLNoh4zDhIhARf94lY8a4DCKZyhE5cO6VseGZqn0y4jJWTMRyTLJ7MGXX6ncsqbcaGtpVtLfYQIkGjJ_SF_2GhoKjbWc6X6OFfjOl2tAevEbjHV1rX1ME22zoHdilNq4ztNQOweEh2augcXj0tSfk8eL8YX4VLG4vr-dni6CIhIqCJGZqKKsU5pFMFHCBFZN8OCCEVHFVxYLzUPIkTVOeci5kmmNSFoKpuCjzaELibW5hO-csVllvdQt2k4Us--SVDbyyv7wG28nW1q_yFssf0zegQSC3gnXXeLRu2azWaLMaofH1_9kfXzN2ug</recordid><startdate>20170606</startdate><enddate>20170606</enddate><creator>Stocchi, Fabrizio</creator><creator>Rascol, Olivier</creator><creator>Hauser, Robert A</creator><creator>Huyck, Susan</creator><creator>Tzontcheva, Anjela</creator><creator>Capece, Rachel</creator><creator>Ho, Tony W</creator><creator>Sklar, Peter</creator><creator>Lines, Christopher</creator><creator>Michelson, David</creator><creator>Hewitt, David J</creator><general>American Academy of Neurology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20170606</creationdate><title>Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease</title><author>Stocchi, Fabrizio ; Rascol, Olivier ; Hauser, Robert A ; Huyck, Susan ; Tzontcheva, Anjela ; Capece, Rachel ; Ho, Tony W ; Sklar, Peter ; Lines, Christopher ; Michelson, David ; Hewitt, David J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3693-540902899eb3859a26ef0829a2a1a7929f462218257772722687be5dc6094cdb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Activities of Daily Living</topic><topic>Adenosine A2 Receptor Antagonists - therapeutic use</topic><topic>Antiparkinson Agents - adverse effects</topic><topic>Antiparkinson Agents - therapeutic use</topic><topic>Dose-Response Relationship, Drug</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Humans</topic><topic>Indans - adverse effects</topic><topic>Indans - therapeutic use</topic><topic>Internationality</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Motor Activity - drug effects</topic><topic>Parkinson Disease - drug therapy</topic><topic>Pyrimidines - adverse effects</topic><topic>Pyrimidines - therapeutic use</topic><topic>Severity of Illness Index</topic><topic>Treatment Failure</topic><topic>Triazoles - adverse effects</topic><topic>Triazoles - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stocchi, Fabrizio</creatorcontrib><creatorcontrib>Rascol, Olivier</creatorcontrib><creatorcontrib>Hauser, Robert A</creatorcontrib><creatorcontrib>Huyck, Susan</creatorcontrib><creatorcontrib>Tzontcheva, Anjela</creatorcontrib><creatorcontrib>Capece, Rachel</creatorcontrib><creatorcontrib>Ho, Tony W</creatorcontrib><creatorcontrib>Sklar, Peter</creatorcontrib><creatorcontrib>Lines, Christopher</creatorcontrib><creatorcontrib>Michelson, David</creatorcontrib><creatorcontrib>Hewitt, David J</creatorcontrib><creatorcontrib>Preladenant Early Parkinson Disease Study Group</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stocchi, Fabrizio</au><au>Rascol, Olivier</au><au>Hauser, Robert A</au><au>Huyck, Susan</au><au>Tzontcheva, Anjela</au><au>Capece, Rachel</au><au>Ho, Tony W</au><au>Sklar, Peter</au><au>Lines, Christopher</au><au>Michelson, David</au><au>Hewitt, David J</au><aucorp>Preladenant Early Parkinson Disease Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease</atitle><jtitle>Neurology</jtitle><addtitle>Neurology</addtitle><date>2017-06-06</date><risdate>2017</risdate><volume>88</volume><issue>23</issue><spage>2198</spage><epage>2206</epage><pages>2198-2206</pages><issn>0028-3878</issn><eissn>1526-632X</eissn><abstract>OBJECTIVE:To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy.
METHODS:This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for <5 years who were not yet receiving L-dopa or dopamine agonists. Patients with a Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 (motor function) score ≥10 and Hoehn & Yahr score ≤3 were randomized 1:1:1:1:1 to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once daily, or placebo. The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS2+3).
RESULTS:The number of patients treated was 1,007. Neither preladenant nor rasagiline was superior to placebo after 26 weeks. The differences vs placebo (95% confidence interval) in UPDRS2+3 scores (with a negative difference indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30), preladenant 5 mg = 1.30 (−0.41, 2.94), preladenant 10 mg = 0.40 (−1.29, 2.11), and rasagiline 1 mg = 0.30 (−1.35, 2.03). Post hoc analyses did not identify a single causal factor that could explain the finding of a failed trial. Preladenant was generally well-tolerated with few patients discontinuing due to adverse events (preladenant 7%, rasagiline 3%, placebo 4%).
CONCLUSIONS:No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial. The lack of efficacy of the active control rasagiline makes it difficult to interpret the results.
CLINICAL TRIAL REGISTRATION:Clinicaltrials.govNCT01155479.
CLASSIFICATION OF EVIDENCE:This study provides Class I evidence that for patients with early PD, preladenant is not effective as monotherapy at the doses studied (2, 5, 10 mg).</abstract><cop>United States</cop><pub>American Academy of Neurology</pub><pmid>28490648</pmid><doi>10.1212/WNL.0000000000004003</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0028-3878 |
| ispartof | Neurology, 2017-06, Vol.88 (23), p.2198-2206 |
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| language | eng |
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| source | MEDLINE; Journals@Ovid Complete; Alma/SFX Local Collection |
| subjects | Activities of Daily Living Adenosine A2 Receptor Antagonists - therapeutic use Antiparkinson Agents - adverse effects Antiparkinson Agents - therapeutic use Dose-Response Relationship, Drug Double-Blind Method Female Humans Indans - adverse effects Indans - therapeutic use Internationality Male Middle Aged Motor Activity - drug effects Parkinson Disease - drug therapy Pyrimidines - adverse effects Pyrimidines - therapeutic use Severity of Illness Index Treatment Failure Triazoles - adverse effects Triazoles - therapeutic use |
| title | Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease |
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