scholarly journals Prospective Clinical Trial Assessing Species-Specific Efficacy of Artemether-Lumefantrine for the Treatment of Plasmodium malariae , Plasmodium ovale , and Mixed Plasmodium Malaria in Gabon

2018 ◽  
Vol 62 (3) ◽  
Author(s):  
Mirjam Groger ◽  
Luzia Veletzky ◽  
Albert Lalremruata ◽  
Chiara Cattaneo ◽  
Johannes Mischlinger ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Antimalarial Activity ◽  
Study Drug ◽  
Plasmodium Malariae ◽  
Fixed Dose ◽  
Plasmodium Ovale ◽  
Content Type ◽  
Primary Endpoints ◽  
Dose Combination ◽  
Species Specific

ABSTRACT Treatment recommendations for Plasmodium malariae and Plasmodium ovale malaria are largely based on anecdotal evidence. The aim of this prospective study, conducted in Gabon, was to systematically assess the efficacy and safety of artemether-lumefantrine for the treatment of patients with uncomplicated P. malariae or P. ovale species monoinfections or mixed Plasmodium infections. Patients with microscopically confirmed P. malariae , P. ovale , or mixed-species malaria with at least one of these two Plasmodium species were treated with an oral, fixed-dose combination of artemether-lumefantrine for 3 consecutive days. The primary endpoints were per-protocol PCR-corrected adequate clinical and parasitological response (ACPR) on days 28 and 42. Tolerability and safety were recorded throughout the follow-up period. Seventy-two participants (42 male and 30 female) were enrolled; 62.5% of them had PCR-corrected mixed Plasmodium infections. Per protocol, PCR-corrected ACPR rates were 96.6% (95% confidence interval [CI], 91.9 to 100) on day 28 and 94.2% (95% CI, 87.7 to 100) on day 42. Considering Plasmodium species independently from their coinfecting species, day 42 ACPR rates were 95.5% (95% CI, 89.0 to 100) for P. falciparum , 100% (exact CI, 84.6 to 100) for P. malariae , 100% (exact CI, 76.8 to 100) for P. ovale curtisi , and 90.9% (95% CI, 70.7 to 100) for P. ovale wallikeri . Study drug-related adverse events were generally mild or moderate. In conclusion, this clinical trial demonstrated satisfying antimalarial activity of artemether-lumefantrine against P. ovale wallikeri , P. ovale curtisi , P. malariae , and mixed Plasmodium infections, with per-protocol efficacies of 90% to 100% and without evident tolerability or safety concerns. (This trial was registered in the clinical study database ClinicalTrials.gov under the identifier NCT02528279.)

A randomized Phase I bioequivalence clinical trial of a pediatric fixed-dose combination antiretroviral reconstitutable suspension in healthy adult volunteers

2012 ◽  
Vol 18 (2) ◽  
pp. 205-212 ◽  
Author(s):  
Fredrick Esseku ◽  
Anjali Joshi ◽  
Yemisi Oyegbile ◽  
Grace Edowhorhu ◽  
Daniel Gbadero ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Healthy Adult ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Dose Combination ◽  
Adult Volunteers

scholarly journals A Single-Dose Combination Study with the Experimental Antimalarials Artefenomel and DSM265 To Determine Safety and Antimalarial Activity against Blood-Stage Plasmodium falciparum in Healthy Volunteers

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
James S. McCarthy ◽  
Thomas Rückle ◽  
Suzanne L. Elliott ◽  
Emma Ballard ◽  
Katharine A. Collins ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Plasma Concentrations ◽  
Parasite Clearance ◽  
Blood Stage ◽  
Content Type ◽  
Dose Combination ◽  
Combination Study ◽  
Study Support ◽  
New Compounds

ABSTRACT Artefenomel and DSM265 are two new compounds that have been shown to be well tolerated and effective when administered as monotherapy malaria treatment. This study aimed to determine the safety, pharmacokinetics, and pharmacodynamics of artefenomel and DSM265 administered in combination to healthy subjects in a volunteer infection study using the Plasmodium falciparum-induced blood-stage malaria model. Thirteen subjects were inoculated with parasite-infected erythrocytes on day 0 and received a single oral dose of artefenomel and DSM265 on day 7. Cohort 1 (n = 8) received 200 mg artefenomel plus 100 mg DSM265, and cohort 2 (n = 5) received 200 mg artefenomel plus 50 mg DSM265. Blood samples were collected to measure parasitemia, gametocytemia, and artefenomel-DSM265 plasma concentrations. There were no treatment-related adverse events. The pharmacokinetic profiles of artefenomel and DSM265 were similar to those of the compounds when administered as monotherapy, suggesting no pharmacokinetic interactions. A reduction in parasitemia occurred in all subjects following treatment (log10 parasite reduction ratios over 48 h [PRR48] of 2.80 for cohort 1 and 2.71 for cohort 2; parasite clearance half-lives of 5.17 h for cohort 1 and 5.33 h for cohort 2). Recrudescence occurred in 5/8 subjects in cohort 1 between days 19 and 28 and in 5/5 subjects in cohort 2 between days 15 and 22. Low-level gametocytemia (1 to 330 female gametocytes/ml) was detected in all subjects from day 14. The results of this single-dosing combination study support the further clinical development of the use of artefenomel and DSM265 in combination as a treatment for falciparum malaria. (This study has been registered at ClinicalTrials.gov under identifier NCT02389348.)

A phase Ib clinical trial on intratumoral administration of autologous CD1c (BDCA-1)+ myeloid dendritic cells (myDC) in combination with ipilimumab (IPI) and avelumab (AVE) plus intravenous low-dose nivolumab (NIVO) in patients with advanced solid tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14012-e14012 ◽  
Author(s):  
Julia Katharina Schwarze ◽  
Gil Awada ◽  
Louise Cras ◽  
Ramses Forsyth ◽  
Ivan Van Riet ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Total Dose ◽  
Solid Tumors ◽  
Low Dose ◽  
Tumor Antigens ◽  
Study Drug ◽  
Advanced Solid Tumors ◽  
Myeloid Dendritic Cells ◽  
Primary Endpoints ◽  
Anti Tumor Activity

e14012 Background: Intratumoral (IT) myDC play a pivotal role in initiating antitumor immune responses and "re-licensing” of antitumor cytotoxic T-lymphocytes within the tumor microenvironment. IT injection of anti-PD-L1 IgG1 mAb AVE and anti-CTLA-4 IgG1 mAb IPI may reduce the number of regulatory T cells and lyse PD-L1+ tumor cells, thereby releasing tumor antigens that can be captured and processed by IT co-administered CD1c (BDCA-1)+ myDC, reinvigorating the cancer immunity cycle. Methods: Patients (pts) with advanced solid tumors who failed standard therapy were eligible for IT injections of ≥1 non-visceral metastasis with IPI (max total dose of 10 mg) and AVE (max total dose of 40 mg) plus IV NIVO (10 mg) on day 1 followed by IT injection of autologous, non-substantially manipulated CD1c (BDCA-1)+ myDC on day 2. Administration of AVE, IPI, and NIVO was repeated every 14 days thereafter. Primary endpoints were safety and feasibility. Repetitive FNA cytology/IHC of treated lesions was performed. Results: In this ongoing trial, 6 pts (3x melanoma, 1x epithelial ovarian carcinoma, 2x triple negative breast carcinoma) were treated with IT injection of a median of 27,2x106 (range 10-43x106) CD1c (BDCA-1)+ myDC and a median of 5 (range 2-10) study drug administrations. At time of this analysis 3 pts are evaluable for response: an ongoing PR ( > 8 months) was documented in a melanoma pt who previously progressed on PD-1 and CTLA-4 inhibitors. In 2 other melanoma pts regression of the injected metastases coincided with progression of non-injected metastases. Adverse events consisted of transient grade(G)2 local pain at injection site in 2 pts, G1 pruritus in 2 pts, G2 pneumonitis in 1 pt, G1 rash in 1 pt, and pruritus and redness of the skin overlaying the injected lesion in 1 pt. Analysis of cytology/IHC results is ongoing. Conclusions: IT injection of autologous CD1c (BDCA-1)+ myDC with IT co-injection of AVE and IPI plus IV low-dose NIVO is feasible and tolerable and resulted in encouraging early signs of anti-tumor activity in injected as well as non-injected lesions. Clinical trial information: NCT03707808.

scholarly journals Evaluation of a fixed-dose combination of benazepril and pimobendan in dogs with congestive heart failure: a randomized non-inferiority clinical trial

2018 ◽  
Vol 19 (1) ◽  
pp. 117 ◽  
Author(s):  
Jonathan N. King ◽  
Atsushi Hirakawa ◽  
Junko Sonobe ◽  
Hiroshi Otaki ◽  
Nobuhiro Sakakibara ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Trial ◽  
Congestive Heart Failure ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Dose Combination

scholarly journals Medical adherence in hypertensive patients treated by triple fixed-dose combination of amlodipine / indapamide / perindopril arginine (results of the Study DOKAZATEL’STVO)

2019 ◽  
Vol 25 (3) ◽  
pp. 285-294
Author(s):  
Zh. D. Kobalava ◽  
E. A. Troitskaya ◽  
M. A. Markova ◽  
Y. V. Khruleva
Keyword(s):  
Medication Adherence ◽  
Study Drug ◽  
Home Blood Pressure ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Targeted Interventions ◽  
Adherence Score ◽  
High Adherence ◽  
Dose Combination ◽  
Design And Methods

Objective. To estimate changes in medication adherence in patients treated with fixed-dose combination of amlodipine / indapamide / perindopril arginine included in DOKAZATEL’STVO observational study.Design and methods. Effects of the fixed-dose combination of amlodipine / indapamide / perindopril arginine on medication adherence were assessed in 1554 patients who filled in the questionnaire at baseline and at the last visit. Primary outcomes of the study included the change in the office and ambulatory (home blood pressure (BP) monitoring) systolic and diastolic BP from baseline to 3 months and rate of the achievement of target BP < 140/90 mmHg after 3-month treatment. Adherence was assessed by special questionnaire.Results. The fixed-dose combination of amlodipine / indapamide / perindopril arginine resulted in the decrease in systolic BP by 39.5 mmHg and diastolic BP by 18.8 mmHg after 3 months. Target office BP < 140/90 mmHg was achieved in 87 %. High adherence at baseline was observed in 7,1 % patients, after 3 months of treatment — in 38,3 % (p < 0,001). Mean adherence score increased from 2,9 ± 1,6 to 5,0 ± 1,1 (p < 0,001). Study drug intake was associated with increase in motivation and awareness from 38 % to 95,4 % and from 19,8 % to 67,3 %, respectively (p < 0,001 for trend).Conclusions. The administration of the fixed-dose combination of amlodipine / indapamide / perindopril arginine was associated with well tolerated BP decrease and significant increase in medication adherence and motivation even in the absence of specific targeted interventions.

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