Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies
Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients...
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| creator | Burri, Christian Yeramian, Patrick D Allen, James L Merolle, Ada Serge, Kazadi Kyanza Mpanya, Alain Lutumba, Pascal Mesu, Victor Kande Betu Ku Bilenge, Constantin Miaka Mia Lubaki, Jean-Pierre Fina Mpoto, Alfred Mpoo Thompson, Mark Munungu, Blaise Fungula Manuel, Francisco Josenando, Théophilo Bernhard, Sonja C Olson, Carol A Blum, Johannes Tidwell, Richard R Pohlig, Gabriele |
| description | Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.
The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.
Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3. |
| doi_str_mv | 10.1371/journal.pntd.0004362 |
| format | Article |
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The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.
Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0004362</identifier><identifier>PMID: 26881924</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Administration, Oral ; Adolescent ; Adult ; Analysis ; Angola ; Antiprotozoal Agents - administration & dosage ; Antiprotozoal Agents - adverse effects ; Benzamidines - administration & dosage ; Benzamidines - adverse effects ; Biology and Life Sciences ; Clinical trials ; Democratic Republic of the Congo - epidemiology ; Disease ; Dosage and administration ; Drug dosages ; Drug therapy ; Drug-Related Side Effects and Adverse Reactions - epidemiology ; Drug-Related Side Effects and Adverse Reactions - pathology ; Female ; Funding ; Humans ; Laboratories ; Male ; Medicine and Health Sciences ; Middle Aged ; Nervous system ; Orphan drugs ; Parasites ; Pentamidine - administration & dosage ; Pentamidine - adverse effects ; Pharmaceutical industry ; Public health ; Research and Analysis Methods ; Stock options ; Studies ; Technical communication ; Treatment Outcome ; Trypanosomiasis ; Trypanosomiasis, African - drug therapy ; Young Adult</subject><ispartof>PLoS neglected tropical diseases, 2016-02, Vol.10 (2), p.e0004362-e0004362</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Burri et al 2016 Burri et al</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Burri C, Yeramian PD, Allen JL, Merolle A, Serge KK, Mpanya A, et al. (2016) Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies. PLoS Negl Trop Dis 10(2): e0004362. doi:10.1371/journal.pntd.0004362</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c629t-9593b4d0792a3f52ff4a82d3d1accfc14a5de1a432cffd7b6710444bd8cae2ee3</citedby><cites>FETCH-LOGICAL-c629t-9593b4d0792a3f52ff4a82d3d1accfc14a5de1a432cffd7b6710444bd8cae2ee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755713/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755713/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26881924$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Franco-Paredes, Carlos</contributor><creatorcontrib>Burri, Christian</creatorcontrib><creatorcontrib>Yeramian, Patrick D</creatorcontrib><creatorcontrib>Allen, James L</creatorcontrib><creatorcontrib>Merolle, Ada</creatorcontrib><creatorcontrib>Serge, Kazadi Kyanza</creatorcontrib><creatorcontrib>Mpanya, Alain</creatorcontrib><creatorcontrib>Lutumba, Pascal</creatorcontrib><creatorcontrib>Mesu, Victor Kande Betu Ku</creatorcontrib><creatorcontrib>Bilenge, Constantin Miaka Mia</creatorcontrib><creatorcontrib>Lubaki, Jean-Pierre Fina</creatorcontrib><creatorcontrib>Mpoto, Alfred Mpoo</creatorcontrib><creatorcontrib>Thompson, Mark</creatorcontrib><creatorcontrib>Munungu, Blaise Fungula</creatorcontrib><creatorcontrib>Manuel, Francisco</creatorcontrib><creatorcontrib>Josenando, Théophilo</creatorcontrib><creatorcontrib>Bernhard, Sonja C</creatorcontrib><creatorcontrib>Olson, Carol A</creatorcontrib><creatorcontrib>Blum, Johannes</creatorcontrib><creatorcontrib>Tidwell, Richard R</creatorcontrib><creatorcontrib>Pohlig, Gabriele</creatorcontrib><title>Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.
The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.
Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.</description><subject>Administration, Oral</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Analysis</subject><subject>Angola</subject><subject>Antiprotozoal Agents - administration & dosage</subject><subject>Antiprotozoal Agents - adverse effects</subject><subject>Benzamidines - administration & dosage</subject><subject>Benzamidines - adverse effects</subject><subject>Biology and Life Sciences</subject><subject>Clinical trials</subject><subject>Democratic Republic of the Congo - epidemiology</subject><subject>Disease</subject><subject>Dosage and administration</subject><subject>Drug dosages</subject><subject>Drug therapy</subject><subject>Drug-Related Side Effects and Adverse Reactions - epidemiology</subject><subject>Drug-Related Side Effects and Adverse Reactions - pathology</subject><subject>Female</subject><subject>Funding</subject><subject>Humans</subject><subject>Laboratories</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Nervous system</subject><subject>Orphan drugs</subject><subject>Parasites</subject><subject>Pentamidine - administration & dosage</subject><subject>Pentamidine - adverse effects</subject><subject>Pharmaceutical industry</subject><subject>Public health</subject><subject>Research and Analysis Methods</subject><subject>Stock options</subject><subject>Studies</subject><subject>Technical communication</subject><subject>Treatment Outcome</subject><subject>Trypanosomiasis</subject><subject>Trypanosomiasis, African - drug therapy</subject><subject>Young Adult</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tu1DAQhiMEoqXwBggsISEuukt8THKDVG1bqFTRii3X1sSHXZfE3toJqLwVb4i3u626EhcoF45nvvkn-e0pite4nGJa4Y_XYYweuunKD3paliWjgjwp9nFD-YRUlD999L5XvEjpuix5w2v8vNgjoq5xQ9h-8efEWqdA3R6iOVgz5BW8RschGRQsugQ7Ruiddt7kDPpqfqGLCB06juMC2RDRVTQw9MYPa_zUxTSg-QALg-adMSvnF2ju1A9vUjpEzmeJyyVkbQJo1jmfW3eZH_XtXdttrkXf8i707rfRu5gz6WXxzEKXzKvtelB8Pz25mn2ZnF98PpsdnU-UIM0waXhDW6bLqiFALSfWMqiJphqDUlZhBlwbDIwSZa2uWlHhkjHW6lqBIcbQg-LtRnfVhSS3bieJq4pWoiY1ycTZhtABruUquh7irQzg5F0gxIWEODjVGVlzaxgvGdiWMS0Aai3qqm7athVWcJy1Pm27jW1vtMqGZpt3RHcz3i3lIvyUrOK8wjQLfNgKxHAzmjTI3iVlug68CePmu2uaQfEfqBBE8IqyjL7boAvIf-G8Dbm5WuPyiFUNpwyLJlPTf1D50aZ3KnhjXY7vFLx_VLA00A3LFLpxcMGnXZBtQBVDStHYB0dwKddjcH8wcj0GcjsGuezNYzcfiu7vPf0L_LgFTw</recordid><startdate>20160216</startdate><enddate>20160216</enddate><creator>Burri, Christian</creator><creator>Yeramian, Patrick D</creator><creator>Allen, James L</creator><creator>Merolle, Ada</creator><creator>Serge, Kazadi Kyanza</creator><creator>Mpanya, Alain</creator><creator>Lutumba, Pascal</creator><creator>Mesu, Victor Kande Betu Ku</creator><creator>Bilenge, Constantin Miaka Mia</creator><creator>Lubaki, Jean-Pierre Fina</creator><creator>Mpoto, Alfred Mpoo</creator><creator>Thompson, Mark</creator><creator>Munungu, Blaise Fungula</creator><creator>Manuel, Francisco</creator><creator>Josenando, Théophilo</creator><creator>Bernhard, Sonja C</creator><creator>Olson, Carol A</creator><creator>Blum, Johannes</creator><creator>Tidwell, Richard R</creator><creator>Pohlig, Gabriele</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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><scope>7X8</scope><scope>7T2</scope><scope>7U2</scope><scope>C1K</scope><scope>M7N</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160216</creationdate><title>Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies</title><author>Burri, Christian ; Yeramian, Patrick D ; Allen, James L ; Merolle, Ada ; Serge, Kazadi Kyanza ; Mpanya, Alain ; Lutumba, Pascal ; Mesu, Victor Kande Betu Ku ; Bilenge, Constantin Miaka Mia ; Lubaki, Jean-Pierre Fina ; Mpoto, Alfred Mpoo ; Thompson, Mark ; Munungu, Blaise Fungula ; Manuel, Francisco ; Josenando, Théophilo ; Bernhard, Sonja C ; Olson, Carol A ; Blum, Johannes ; Tidwell, Richard R ; Pohlig, Gabriele</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c629t-9593b4d0792a3f52ff4a82d3d1accfc14a5de1a432cffd7b6710444bd8cae2ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Administration, Oral</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Analysis</topic><topic>Angola</topic><topic>Antiprotozoal Agents - 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We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.
The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.
Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26881924</pmid><doi>10.1371/journal.pntd.0004362</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | PLoS neglected tropical diseases, 2016-02, Vol.10 (2), p.e0004362-e0004362 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
| recordid | cdi_plos_journals_1773768282 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Public Library of Science (PLoS) |
| subjects | Administration, Oral Adolescent Adult Analysis Angola Antiprotozoal Agents - administration & dosage Antiprotozoal Agents - adverse effects Benzamidines - administration & dosage Benzamidines - adverse effects Biology and Life Sciences Clinical trials Democratic Republic of the Congo - epidemiology Disease Dosage and administration Drug dosages Drug therapy Drug-Related Side Effects and Adverse Reactions - epidemiology Drug-Related Side Effects and Adverse Reactions - pathology Female Funding Humans Laboratories Male Medicine and Health Sciences Middle Aged Nervous system Orphan drugs Parasites Pentamidine - administration & dosage Pentamidine - adverse effects Pharmaceutical industry Public health Research and Analysis Methods Stock options Studies Technical communication Treatment Outcome Trypanosomiasis Trypanosomiasis, African - drug therapy Young Adult |
| title | Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T14%3A26%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Efficacy,%20Safety,%20and%20Dose%20of%20Pafuramidine,%20a%20New%20Oral%20Drug%20for%20Treatment%20of%20First%20Stage%20Sleeping%20Sickness,%20in%20a%20Phase%202a%20Clinical%20Study%20and%20Phase%202b%20Randomized%20Clinical%20Studies&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Burri,%20Christian&rft.date=2016-02-16&rft.volume=10&rft.issue=2&rft.spage=e0004362&rft.epage=e0004362&rft.pages=e0004362-e0004362&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0004362&rft_dat=%3Cgale_plos_%3EA479534169%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1766265734&rft_id=info:pmid/26881924&rft_galeid=A479534169&rft_doaj_id=oai_doaj_org_article_85fe4504afb44d6aa8d68789bbb6f651&rfr_iscdi=true |