Chlorproguanil-dapsone: effective treatment for uncomplicated falciparum malaria.

Pyrimethamine-sulfadoxine, the first choice for uncomplicated falciparum malaria in Africa, exerts strong selection pressure for resistance because of its slow elimination. It is likely that resistance will emerge rapidly, and there is no widely affordable replacement. Chlorproguanil-dapsone is cheap, rapidly eliminated, more potent than pyrimethamine-sulfadoxine, and could be introduced in the near future to delay the onset of antifolate resistance and as "salvage therapy" for pyrimethamine-sulfadoxine failure. A total of 448 children were randomly allocated (double blind) to either a single dose of pyrimethamine-sulfadoxine or to one of two chlorproguanil-dapsone regimens: a single dose or three doses at 24-h intervals. Reinfections are clinically indistinguishable from recrudescence and are more likely after treatment with rapidly eliminated drugs; we measured the incidence of parasitemia in 205 initially aparasitemic children to allow comparison with the three treatment groups. The patients and a community surveillance group were followed up for 28 days. At the study end point, 31.2% (95% confidence interval, 24.9-38.0) of the community surveillance group subjects were parasitemic, compared with subjects in the treatment groups, whose rates of parasitemia were 40.8% (32.9-49.0; relative risk [RR], 1.31 [0.99-1.73]) after triple-dose chlorproguanil-dapsone, 19.7% (13.5-27.2; RR, 0.63 [0.43-0.93]) after pyrimethamine-sulfadoxine, and 65.6% (57.5-73.0; RR, 2.10 [1.66-2.65]) after single-dose chlorproguanil-dapsone. Pyrimethamine-sulfadoxine and triple-dose chlorproguanil-dapsone were effective treatments. Pyrimethamine-sulfadoxine provided chemoprophylaxis during follow-up because of its slow elimination. Triple-dose chlorproguanil-dapsone should now be developed in an attempt to reduce the rate of emergence of antifolate resistance in Africa and for affordable salvage therapy in cases of pyrimethamine-sulfadoxine failure.

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Cyclandelate in the Prophylaxis of Migraine

Cephalalgia ◽

10.1046/j.1468-2982.1996.1606441.x ◽

1996 ◽

Vol 16 (6) ◽

pp. 441-447 ◽

Cited By ~ 30

Author(s):

HC Diener ◽

M F”h ◽

C laccarino ◽

P Wessely ◽

H Isler ◽

...

Keyword(s):

Statistical Significance ◽

Platelet Activating Factor ◽

Baseline Period ◽

Comparable Efficacy ◽

Double Blind ◽

Treatment Groups ◽

Adverse Experiences ◽

First Choice ◽

The Difference ◽

Better Than

Cyclandelate inhibits calcium-induced contraction of vascular smooth muscle cells, platelet aggregation induced by thrombin, platelet-activating-factor and adenosine, and also suppresses a provoked 5HT release from platelets. This pharmacological profile suggests that cyclandelate may have a potential prophylactic effect in migraine. To test this hypothesis, a double-blind multicentre study was performed in 214 patients to investigate the efficacy and tolerability of cyclandelate compared to placebo and propranolol. After a 4-week baseline period, eligible patients (randomization 3:2:3) were treated for 12 weeks with daily doses of 1.200 mg cyclandelate ( n=81), placebo ( n=55) or 120 mg propranolol ( n=78). The number of migraine attacks (350% responders) and the migraine duration/month were compared based on the difference between baseline and the last 4 weeks of prophylactic treatment. The percentage of patients with a reduction in migraine attacks of 350% treated with cyclancelate (37.0%) or propranolol (42.3%) was not significantly superior to placebo (30.9%; P>0.025). The mean duration of migraine in hours (h) per month decreased in both active treatment groups (cyclandelate: 36.8h, p=0.046; propranolol: 34.4 h, p=0.039) compared to placebo (13.7 h) without reaching statistical significance (alpha/2=0.025). The clinical efficacy of cyclandelate and propranolol was comparable. Adverse experiences were reported by 13 patients (16.0%) treated with cyclandelate, by 5 patients (9.1%) treated with placebo and by 19 patients (24.4%) treated with propranolol. These were drug-related in 7.1% ( n=6) of patients treated with cyclandelate and in 9% ( n=7) of patients treated with propranolol. In summary, cyclandelate has a comparable efficacy to that of propranolol an established drug of first choice in the prophylaxis of migraine. Both drugs were better than placebo, but not significantly so. Both active treatments were well tolerated. ÿ box

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Single dose artemisinin-mefloquine versus mefloquine alone for uncomplicated falciparum malaria

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1016/s0035-9203(97)90221-2 ◽

1997 ◽

Vol 91 (2) ◽

pp. 191-194 ◽

Cited By ~ 11

Author(s):

Le Ngoc Hung ◽

Peter J. de Vries ◽

Le Thi Diemn Thuy ◽

Bich Lien ◽

Ho Phi Long ◽

...

Keyword(s):

Single Dose ◽

Falciparum Malaria ◽

Uncomplicated Falciparum Malaria

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Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial

Malaria Journal ◽

10.1186/1475-2875-7-91 ◽

2008 ◽

Vol 7 (1) ◽

pp. 91 ◽

Cited By ~ 8

Author(s):

Pierre-Blaise Matsiégui ◽

Michel A Missinou ◽

Magdalena Necek ◽

Elie Mavoungou ◽

Saadou Issifou ◽

...

Keyword(s):

Falciparum Malaria ◽

Controlled Trial ◽

Uncomplicated Falciparum Malaria ◽

Double Blind ◽

Antipyretic Effect ◽

Double Blind Placebo

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HerbaArtemisiae annuaetea preparation compared to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in adults: a randomized double-blind clinical trial

Tropical Doctor ◽

10.1258/td.2007.060184 ◽

2008 ◽

Vol 38 (2) ◽

pp. 113-116 ◽

Cited By ~ 21

Author(s):

Christoph H Blanke ◽

Godson B Naisabha ◽

Mussa B Balema ◽

Godfrey M Mbaruku ◽

Lutz Heide ◽

...

Keyword(s):

Clinical Trial ◽

Falciparum Malaria ◽

Uncomplicated Falciparum Malaria ◽

Double Blind ◽

Double Blind Clinical Trial

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A randomized, single-dose, pharmacokinetic equivalence study comparing MB02 (proposed biosimilar) and reference bevacizumab in healthy Japanese male volunteers

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-021-04324-z ◽

2021 ◽

Author(s):

Takashi Eto ◽

Yuji Karasuyama ◽

Verónica González ◽

Ana Del Campo García

Keyword(s):

Single Dose ◽

Japanese Population ◽

Post Dose ◽

Double Blind ◽

Time Curve ◽

Treatment Groups ◽

Male Volunteers ◽

Japanese Male ◽

Parallel Group

Abstract Purpose MB02 is a biosimilar to bevacizumab that has demonstrated similar physicochemical and functional properties in in vitro studies to the reference bevacizumab (Avastin®). This study aims to assess the pharmacokinetic (PK) similarity of MB02 to the reference bevacizumab in Japanese population. Methods This double-blind, randomized, parallel-group, single-dose PK study, was performed in healthy Japanese male volunteers. Subjects were equally randomized (1:1) to receive a single (3 mg/kg) IV dose of MB02 or reference bevacizumab. PK assessments were done up to 70 days post-dose. Non-compartmental parameters were calculated. PK similarity was determined using predefined equivalence range (0.80–1.25) for the area under the serum concentration–time curve from time 0 extrapolated to infinity (AUC0–∞). Immunogenicity samples were taken pre-dose and up to day 70. Safety was assessed throughout the study. Results In total, 48 subjects (24 in each treatment group) were dosed. Consequently to the observed similar PK profile, the 90% confidence interval for the geometric means ratio for the primary PK endpoint, AUC0–∞, was within the predefined equivalence range (0.981–1.11). Forty-seven treatment-emergent adverse events (TEAEs) were reported in 20 subjects (41.7%) with comparable incidence among MB02 and reference bevacizumab groups (22 and 25, respectively), none of them was severe or serious. Anti-drug antibodies incidence was low and similar between treatment groups. Conclusions Pharmacokinetic similarity of MB02 to reference bevacizumab was evidenced in Japanese healthy subjects, with comparable safety and immunogenicity profile between treatments. This study supports the biosimilarity of MB02 to reference bevacizumab in Japanese population. ClinicalTrials.gov identifier: NCT04238650.

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