Delving into the Latest Updates on Amodiaquine/Artesunate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

AS/AQ, ASAQ, ASAQ Winthrop

+ [6]

Target

ATP2A1 x SERCA2

Action

inhibitors

Mechanism

ATP2A1 inhibitors(Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 inhibitors), SERCA2 inhibitors(Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 inhibitors)

Therapeutic Areas

Infectious Diseases

Active Indication

Malaria

Inactive Indication

Malaria, FalciparumMalaria, Vivax

Originator Organization

Drugs for Neglected Diseases initiative

Active Organization

Sanofi-Aventis U.S. LLC

Inactive Organization

Sanofi

License Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC39H50ClN3O9

InChIKeyFNDVKMABQZJHKI-GMDKYCAISA-N

CAS Registry944945-14-6

Malaria remains a public health concern, despite efforts that are invested in the disease control. The Democratic Republic of the Congo (DRC) is one of the most affected countries in Sub Saharan Africa. Artemisinin-based combination treatments (ACTs) are recommended for the treatment of uncomplicated malaria. However, reported cases of mutations that confer to Plasmodium falciparum resistance to artemisinin (the main component of ACTs) constitute a threat to malaria control, particularly in Sub Saharan Africa. Therefore, the recommendation of the World Health Organization to conduct regularly test efficacy studies in endemic countries is paramount.
The purpose of this trial is to assess efficacy and safety of artesunate-amodiaquine (ASAQ Winthrop®) and artemether-lumefantrine (Coartem Dispersible®) at day 28 for the treatment of uncomplicated Plasmodium falciparum malaria in eight surveillance sites around DRC.

Start Date01 May 2023

Sponsor / Collaborator

Global Fund

[+1]

PACTR202301796134887

/ RecruitingPhase 4IIT

EFFICACY AND SAFETY OF ARTEMETHER LUMEFANTRINE, PYRONARIDINE ARTESUNATE, ARTESUNATE AMODIAQUINE, AND DIHYDROARTEMISININ PIPERAQUINE FOR THE TREATMENT OF UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA IN CHILDREN IN UGANDA

Start Date01 Nov 2022

Sponsor / Collaborator-

NCT05550909

/ CompletedPhase 2IIT

A Five-arm Trial Comparing Artesunate-amodiaquine and Artemether-lumefantrine-amodiaquine With or Without Single-dose Primaquine to Reduce P. Falciparum Transmission in Mali

The purpose of this study is to compare the gametocytocidal and transmission reducing activity of artesunate-amodiaquine (ASAQ) and artemether-lumefantrine-amodiaquine (ALAQ) with and without a single dose of 0.25mg/kg primaquine (PQ). Outcome measures will include infectivity to mosquitoes at 2, 7 and 14 days after treatment, gametocyte density throughout follow-up, and safety measures including haemoglobin density and the frequency of adverse events.

Start Date17 Oct 2022

Sponsor / Collaborator

London School of Hygiene & Tropical Medicine

100 Clinical Results associated with Amodiaquine/Artesunate

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100 Translational Medicine associated with Amodiaquine/Artesunate

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100 Patents (Medical) associated with Amodiaquine/Artesunate

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238

Literatures (Medical) associated with Amodiaquine/Artesunate

01 Feb 2025·The Lancet Microbe

Artemether–lumefantrine–amodiaquine or artesunate–amodiaquine combined with single low-dose primaquine to reduce Plasmodium falciparum malaria transmission in Ouélessébougou, Mali: a five-arm, phase 2, single-blind, randomised controlled trial

Article

Author: Youssouf, Ahamadou ; Dicko, Oumar M ; Dicko, Yahia ; Teelen, Karina ; Diarra, Richard S ; Dembele, Adama ; Traore, Sekou F ; Keita, Sekouba ; Vanheer, Leen N ; Samake, Siaka ; Sanogo, Koualy ; Sinaba, Youssouf ; Niambele, Sidi M ; Drakeley, Chris ; Maguiraga, Seydina O ; Dicko, Alassane ; Smit, Merel J ; Stone, William ; Diallo, Makonon ; Dondorp, Arjen ; Sacko, Adama ; Mahamar, Almahamoudou

BACKGROUNDTriple artemisinin-based combination therapies (TACTs) can delay the spread of antimalarial drug resistance. Artesunate-amodiaquine is widely used for uncomplicated Plasmodium falciparum malaria. We therefore aimed to determine the safety and efficacy of artemether-lumefantrine-amodiaquine and artesunate-amodiaquine with and without single low-dose primaquine for reducing gametocyte carriage and transmission to mosquitoes.METHODSWe did a five-arm, single-blind, phase 2 randomised controlled trial at the Ouélessébougou Clinical Research Unit of the Malaria Research and Training Centre of the University of Sciences, Techniques and Technologies of Bamako in Mali. Eligible participants were aged 10-50 years, with asymptomatic P falciparum microscopy-detected gametocyte carriage. Eligible participants were randomly allocated (1:1:1:1:1) to receive either artemether-lumefantrine, artemether-lumefantrine-amodiaquine, artemether-lumefantrine-amodiaquine plus primaquine, artesunate-amodiaquine, or artesunate-amodiaquine plus primaquine. Treatment regimens were administered on days 0, 1, and 2; primaquine was given as a single dose on day 0. All staff except the trial pharmacist and participants were masked to the treatment allocation. The primary outcome was the median percentage change in mosquito infection rate between pretreatment and 2 days after treatment initiation, assessed by direct membrane feeding assay. Data were analysed using a per-protocol analysis. This study is registered with ClinicalTrials.gov, NCT05550909.FINDINGSBetween Oct 16, 2022, and Dec 28, 2022, a total of 1249 individuals were screened; of whom, 100 were enrolled and randomly assigned to one of the five treatment groups (20 per group). Before treatment, 61 (61%) of 100 participants were infectious to mosquitoes, with a median of 7·3% (IQR 3·2 to 23·5) of mosquitoes becoming infected. Among infectious participants, the median percentage reduction in mosquito infection rate between pretreatment and 2 days after treatment was 100% (IQR 100 to 100) in the artemether-lumefantrine (p=0·0018), artemether-lumefantrine-amodiaquine (p=0·0018), and artemether-lumefantrine-amodiaquine plus primaquine (p=0·0009) treatment groups. In the artesunate-amodiaquine group the median percentage reduction in mosquito infection rate was only 32% (IQR -10·9 to 79·4; p=0·19), whereas a 100% median reduction was seen in the artesunate-amodiaquine plus primaquine group (IQR 100 to 100; p=0·0009). At day 2, two (10%) of 20 participants in the artemether-lumefantrine group, two (11%) of 19 in the artemether-lumefantrine-amodiaquine group, and 15 (75%) of 20 in the artesunate-amodiaquine group infected any number of mosquitoes whereas no infected mosquitoes were observed at this timepoint in the groups with primaquine. 85 (85%) of 100 participants had a total of 262 adverse events during follow-up; of which, 181 (69%) were categorised as mild and 81 (31%) as moderate. No serious adverse events were reported.INTERPRETATIONOur findings support the effectiveness of artemether-lumefantrine alone or as part of TACT for preventing nearly all human-mosquito malaria parasite transmission within 48 h. By contrast, substantial transmission was observed following treatment with artesunate-amodiaquine. The addition of a single low dose of primaquine blocks transmission to mosquitoes rapidly regardless of schizonticide.FUNDINGBill & Melinda Gates Foundation.

01 Jan 2025·Case Reports in Infectious Diseases

Neonatal Survival Following Spontaneous Maternal Recovery From Ebola Virus Disease in a Resource‐Limited Setting in Western Democratic Republic of the Congo

Article

Author: Sengeyi-Mushengezi-Amani, Dieudonné ; Tsongo-Kibendelwa, Zacharie ; Barhwamire-Kabesha, Théophile ; Imani-Musimwa, Prince ; Feza-Malira, Micheline ; Grant, Emilie ; Bitwe-Mihanda, Richard ; Kavira-Malengera, Celine ; Mbala-Kingebeni, Placide ; Fraterne-Muhayangabo, Rigo ; Claris-Mwatsi, Ines ; Ververs, Mija ; Mukadi-Bamuleka, Daniel ; Kitenge-Omasumbu, Richard ; Sihali-Kyolov, Juakali ; Nyakio-Ngeleza, Olivier

Background: Pregnancy induces physiological decline in maternal immunity. Ebola virus disease (EVD) in pregnancy is associated with obstetrical complications, and vaccination in early pregnancy is recommended, but may not be without risk.Case Presentation: We described neonatal survival after spontaneous maternal EVD recovery. This neonate was born to a 25‐year‐old mother admitted to an Ebola Treatment Unit (ETU) in July, 2020, after 11 days of symptoms. She was vaccinated with rVSV‐ZEBOV three days before symptom onset and her real‐time polymerase chain of reaction (RT‐PCR) results confirmed EVD and malarial infection two days after, but she refused hospitalization. She was treated at home with PO ASAQ, amoxicillin, paracetamol, albendazole, omeprazole, and papaverine. Eleven days later, due to clinical deterioration and onset of vaginal hemorrhage, she finally accepted to be transferred in ETU. She was Parity 2, fetal age at admission was 5 weeks and 3 days. Upon admission, her EVD PCR measured NP 26.3 and GP 32.9. She did not receive monoclonal therapy against Ebola infection due to stock shortage. She received intravenous, artesunate, ceftriaxone, and papaverine. She experienced spontaneous resolution of EVD 18 days after symptom onset and was discharged. At 40 weeks gestation, seven and a half months after EVD recovery, she delivered a healthy female infant, APGAR 10/10/10, weighing 3450 g. Maternal blood, adnexal, and newborn blood samples were RT‐PCR negative, and the mother and the baby were discharged after 14 days. At our last follow‐up, in June 2023 (2 years, 3 months after delivery), the mother and the baby were in good health.Conclusion: Neonatal survival following spontaneous maternal recovery from EVD in the first trimester of gestation is rare but possible, even in the context of limited clinical resources for treatment.

01 Dec 2024·Current Drug Metabolism

Development of Hot Melt Extruded Co-Formulated Artesunate and Amodiaquine- Soluplus^® Solid Dispersion System in Fixed-Dose Form: Amorphous State Characterization and Pharmacokinetic Evaluation

Article

Author: Fule, Ritesh ; Almoutairi, Meshal Meteab Majed ; Warsi, Musarrat Husain ; Elhassan, Gamal Osman ; Amin, Purnima ; Kaleem, Mohammed ; Mujtaba, Md Ali

Introduction:This study aims to develop co-amorphous Solid Dispersion (SD) system containing antimalarials Artesunate (ARS) and Amodiaquine (AMQ) to improve its oral bioavailability employing the Hot Melt Extrusion (HME) technique. Soluplus® was selected as a polymeric excipient, whereas Lutrol F127, Lutrol F68, TPGS, and PEG400 as surfactants were incorporated along with Soluplus® to enhance extrudability, improve hydrophilicity, and improve the blend viscosity during HME. Soluplus® with surfactant combination successfully stabilizes both drugs during extrusion by generating SD because of its lower glass transition temperature (Tg) and viscoelastic behavior.Methods:Physicochemical characterizations were performed using FTIR, DSC, TGA, and XRD, which confirmed the amorphousization of drugs in the SD system. The molecular level morphology of the optimized formulation was quantified using high-resolution techniques such as Atomic-Force Microscopy (AFM), Raman spectral, and mapping analysis. The transition of the crystalline drugs into a stable amorphous form has been demonstrated by 1H-NMR and 2D-NMR studies. The in vivo pharmacokinetics study in rats showed that the SD-containing drug-Soluplus-TPGS (FDC10) formulation has 36.63-56.13 (ARS-AMQ) folds increase in the Cmax and 41.87-54.34 (ARS-AMQ) folds increase AUC (0–72) as compared to pure drugs.Results:Pharmacokinetic analysis shows that a fixed-dose combination of 50:135 mg of both APIs (ARSAMQ) significantly increased oral bioavailability by elevating Cmax and AUC, in comparison to pure APIs and also better than the marketed product Coarsucam®. .Conclusion:Therefore, the developed melt extruded co-amorphous formulation has enhanced bioavailability and has more effectiveness than the marketed product Coarsucam®.

100 Deals associated with Amodiaquine/Artesunate

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External Link

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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Malaria	-	Sanofi-Aventis U.S. LLC	-

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Malaria, Vivax	Preclinical	Brazil	Sanofi	01 Jan 2012
Malaria	Preclinical	France	Sanofi	01 Jun 2006
Malaria, Falciparum	Preclinical	Cameroon	Sanofi	01 Mar 2006
Malaria, Falciparum	Preclinical	Madagascar	Sanofi	01 Mar 2006
Malaria, Falciparum	Preclinical	Mali	Sanofi	01 Mar 2006
Malaria, Falciparum	Preclinical	Senegal	Sanofi	01 Mar 2006

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05550909 (five-arm, phase 2, Pubmed \| Lancet Microbe)	Phase 2	Malaria, Falciparum	100	Artemether-lumefantrine	eoyoauvgki(fnyawistpn) = 85 (85%) of 100 participants had a total of 262 adverse events during follow-up; of which, 181 (69%) were categorised as mild and 81 (31%) as moderate. No serious adverse events were reported. unvcswfauo (tublpbqtbx )	Positive	01 Dec 2024
				Artemether-lumefantrine-amodiaquine
NCT04565184 (Pubmed \| BMC Infect Dis)	Phase 4	Malaria, Falciparum	242	Artesunate-amodiaquine	utbwqkfeyf(qqlvijrutr) = Expected mild to moderate adverse events were reported in both arms [AS-AQ = 83 (84.7%) versus AL = 99 (86.1%), P = 0.774]. The most common adverse events included: transient changes of hematologic indices and fever. ecacfcsctr (nhxwonugao )	Positive	21 Feb 2022
				Artemether-lumefantrine
NCT04370977 (Pubmed \| Malar J)	Phase 4	Malaria, Falciparum First line	630	Artemether-lumefantrine	ptzgrofbty(szhzvvednn) = qqyljsmapy hskjyiezqd (xtlpuebopp, 95.6 - 99.2) View more	-	02 Oct 2021
				Amodiaquine-artesunate	ptzgrofbty(szhzvvednn) = muyfmbodhl hskjyiezqd (xtlpuebopp, 97.9 - 100) View more
NCT00297882 (CTgov)	Phase 3	Malaria	816	2. Amodiaquine-Artesunate (AQ-AS)	vklhtcwljm(hxiqnfdxce) = pvrxfpwhqv jxondovrcu (fchotmuudw, ynlrloknhs - wtcgrnaghz) View more	-	08 Jun 2021
NCT03431714 (Pubmed \| Malar J)	Phase 4	Malaria, Falciparum	724	artesunate-amodiaquine	bfdmhgwnea(jjdpwniekz) = xtcqzkfiqx arzopnknvq (hxnbwgwarj )	-	25 Mar 2019
				dihydroartemisinin-piperaquine	bfdmhgwnea(jjdpwniekz) = gxlvrrnbkr arzopnknvq (hxnbwgwarj )
NCT01967472 (Pubmed \| Malar J)	Not Applicable	Malaria	784	Artemether-lumefantrine	(rdlhmemdni) = tfinocmidj tpszxdfjed (ieopebncsj ) View more	-	04 Jun 2018
				Amodiaquine-artesunate	(rdlhmemdni) = jnemkjdjxc tpszxdfjed (ieopebncsj ) View more
NCT01378286 (Pubmed \| Clin Infect Dis) Manual	Phase 3	Malaria, Vivax	380	Artesunate-Amodiaquine	qbeorbrsln(uaxuhnlnjb) = mwxzcbdpdo ehnviqzuwh (ghklibgoyo ) View more	Superior	15 Jan 2017
				Chloroquine	qbeorbrsln(uaxuhnlnjb) = duxlykmbpq ehnviqzuwh (ghklibgoyo ) View more
NCT00699920 (not provided, Pubmed \| PLoS One)	Phase 4	Malaria	413	artesunate-amodiaquine	mlywjogebl(sjtbqvgbqi) = uqmaslvtqt ufvtfvubgr (gtylvywmvq, [ - 0.028; 0.037])	Positive	01 Dec 2014
				artemether-lumefantrine	mlywjogebl(sjtbqvgbqi) = mysziygjpa ufvtfvubgr (gtylvywmvq )
PACTR2009010000911750 \| NCT00393679 (Pubmed \| PLoS Med)	Phase 3	Malaria	4,112	amodiaquine-artesunate (ASAQ)	echihkgpca(dizvoybjoz) = rescszeyua vsvnvhdtgm (potbrimxow ) View more	-	01 Nov 2011
				dihydroartemisinin-piperaquine (DHAPQ)	echihkgpca(dizvoybjoz) = gelatrnvxy vsvnvhdtgm (potbrimxow ) View more