Comparison of the safety and efficacy of fixed-dose combination of arterolane maleate and piperaquine phosphate with chloroquine in acute, uncomplicated Plasmodium vivax malaria

A phase III, multicentric, open-label study

Neena Valecha, Deepali Savargaonkar, Bina Srivastava, B. H.Krishnamoorthy Rao, Santanu K. Tripathi, Nithya Gogtay, Sanjay Kumar Kochar, Nalli Babu Vijaya Kumar, Girish Chandra Rajadhyaksha, Jitendra D. Lakhani, Bhagirath B. Solanki, Rajinder K. Jalali, Sudershan Arora, Arjun Roy, Nilanjan Saha, Sunil S. Iyer, Pradeep Sharma, Anupkumar R. Anvikar

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Chloroquine has been the treatment of choice for acute vivax malaria for more than 60 years. Malaria caused by Plasmodium vivax has recently shown resistance to chloroquine in some places. This study compared the efficacy and safety of fixed dose combination (FDC) of arterolane maleate and piperaquine phosphate (PQP) with chloroquine in the treatment of uncomplicated vivax malaria. Methods: Patients aged 13-65 years with confirmed mono-infection of P. vivax along with fever or fever in the previous 48 h were included. The 317 eligible patients were randomly assigned to receive FDC of arterolane maleate and PQP (n = 159) or chloroquine (n = 158) for 3 days. Primaquine was given as an anti-relapse measure on day 3 and continued for 14 consecutive days. Primary efficacy analysis included assessment of the proportion of aparasitaemic and afebrile patients at 72 h. Safety endpoints were analysis of adverse events, vital signs, laboratory data, and abnormalities on electrocardiograph. Patients participated in the study for at least 42 days. Results: In per protocol population, the proportion of aparasitaemic and afebrile patients at 72 h was 100 % (140/140) in the FDC of arterolane maleate and PQP group, and 99.3 % (145/146) in the chloroquine group (Fisher, p > 0.9999). In intent to treat population, the corresponding value was reported to be 96.9 % (154/159) in the FDC of arterolane maleate and PQP group and 98.7 % (156/158) in the chloroquine group (Fisher, p = 0.4479). The median parasite clearance time was 24 h in FDC of arterolane maleate and PQP group and 26 h in chloroquine group (Log-rank, p = 0.2264). Similarly, median fever clearance time was 24 h in both the groups (Log-rank, p = 0.7750). In PP population, day 28 cure rates were 100 % in both the groups (95 % CI (96.52, 100.0 for FDC of arterolane maleate and PQP and 96.73, 100.0 in chloroquine group)). Incidence of adverse events was 82.4 % in the FDC of arterolane maleate and PQP group and 85.4 % in the chloroquine group. Most of the adverse events were mild to moderate in intensity. The commonly reported clinical adverse events in the FDC of arterolane maleate and PQP versus chloroquine group were vomiting (5.0 vs 5.1 %), headache (1.3 vs 3.2 %) and prolonged QT (1.9 vs 3.2 %). No deaths were reported. The pharmacokinetic analysis indicates that arterolane maleate is well absorbed and has a relatively short t1/2 of 3.2 h. Piperaquine is also well absorbed after oral administration with a t1/2 of about 228.33 h. Conclusions: The study showed that FDC of arterolane maleate and PQP effectively cured vivax malaria and attained acceptable level of cure up to day 28. Both the groups showed similar safety profile. Trial Registration Clinical Trial Registry India: CTRI/2011/11/002129.

Original languageEnglish
Article number42
JournalMalaria Journal
Volume15
Issue number1
DOIs
Publication statusPublished - 27-01-2016
Externally publishedYes

Fingerprint

Vivax Malaria
Chloroquine
Safety
Phosphates
Fever
chloroquine diphosphate
piperaquine
arterolane
maleic acid
Primaquine
Population
Plasmodium vivax
Vital Signs
Vomiting
Headache
Oral Administration
Registries
India
Electrocardiography
Parasites

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Infectious Diseases

Cite this

Valecha, Neena ; Savargaonkar, Deepali ; Srivastava, Bina ; Rao, B. H.Krishnamoorthy ; Tripathi, Santanu K. ; Gogtay, Nithya ; Kochar, Sanjay Kumar ; Kumar, Nalli Babu Vijaya ; Rajadhyaksha, Girish Chandra ; Lakhani, Jitendra D. ; Solanki, Bhagirath B. ; Jalali, Rajinder K. ; Arora, Sudershan ; Roy, Arjun ; Saha, Nilanjan ; Iyer, Sunil S. ; Sharma, Pradeep ; Anvikar, Anupkumar R. / Comparison of the safety and efficacy of fixed-dose combination of arterolane maleate and piperaquine phosphate with chloroquine in acute, uncomplicated Plasmodium vivax malaria : A phase III, multicentric, open-label study. In: Malaria Journal. 2016 ; Vol. 15, No. 1.
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title = "Comparison of the safety and efficacy of fixed-dose combination of arterolane maleate and piperaquine phosphate with chloroquine in acute, uncomplicated Plasmodium vivax malaria: A phase III, multicentric, open-label study",
abstract = "Background: Chloroquine has been the treatment of choice for acute vivax malaria for more than 60 years. Malaria caused by Plasmodium vivax has recently shown resistance to chloroquine in some places. This study compared the efficacy and safety of fixed dose combination (FDC) of arterolane maleate and piperaquine phosphate (PQP) with chloroquine in the treatment of uncomplicated vivax malaria. Methods: Patients aged 13-65 years with confirmed mono-infection of P. vivax along with fever or fever in the previous 48 h were included. The 317 eligible patients were randomly assigned to receive FDC of arterolane maleate and PQP (n = 159) or chloroquine (n = 158) for 3 days. Primaquine was given as an anti-relapse measure on day 3 and continued for 14 consecutive days. Primary efficacy analysis included assessment of the proportion of aparasitaemic and afebrile patients at 72 h. Safety endpoints were analysis of adverse events, vital signs, laboratory data, and abnormalities on electrocardiograph. Patients participated in the study for at least 42 days. Results: In per protocol population, the proportion of aparasitaemic and afebrile patients at 72 h was 100 {\%} (140/140) in the FDC of arterolane maleate and PQP group, and 99.3 {\%} (145/146) in the chloroquine group (Fisher, p > 0.9999). In intent to treat population, the corresponding value was reported to be 96.9 {\%} (154/159) in the FDC of arterolane maleate and PQP group and 98.7 {\%} (156/158) in the chloroquine group (Fisher, p = 0.4479). The median parasite clearance time was 24 h in FDC of arterolane maleate and PQP group and 26 h in chloroquine group (Log-rank, p = 0.2264). Similarly, median fever clearance time was 24 h in both the groups (Log-rank, p = 0.7750). In PP population, day 28 cure rates were 100 {\%} in both the groups (95 {\%} CI (96.52, 100.0 for FDC of arterolane maleate and PQP and 96.73, 100.0 in chloroquine group)). Incidence of adverse events was 82.4 {\%} in the FDC of arterolane maleate and PQP group and 85.4 {\%} in the chloroquine group. Most of the adverse events were mild to moderate in intensity. The commonly reported clinical adverse events in the FDC of arterolane maleate and PQP versus chloroquine group were vomiting (5.0 vs 5.1 {\%}), headache (1.3 vs 3.2 {\%}) and prolonged QT (1.9 vs 3.2 {\%}). No deaths were reported. The pharmacokinetic analysis indicates that arterolane maleate is well absorbed and has a relatively short t1/2 of 3.2 h. Piperaquine is also well absorbed after oral administration with a t1/2 of about 228.33 h. Conclusions: The study showed that FDC of arterolane maleate and PQP effectively cured vivax malaria and attained acceptable level of cure up to day 28. Both the groups showed similar safety profile. Trial Registration Clinical Trial Registry India: CTRI/2011/11/002129.",
author = "Neena Valecha and Deepali Savargaonkar and Bina Srivastava and Rao, {B. H.Krishnamoorthy} and Tripathi, {Santanu K.} and Nithya Gogtay and Kochar, {Sanjay Kumar} and Kumar, {Nalli Babu Vijaya} and Rajadhyaksha, {Girish Chandra} and Lakhani, {Jitendra D.} and Solanki, {Bhagirath B.} and Jalali, {Rajinder K.} and Sudershan Arora and Arjun Roy and Nilanjan Saha and Iyer, {Sunil S.} and Pradeep Sharma and Anvikar, {Anupkumar R.}",
year = "2016",
month = "1",
day = "27",
doi = "10.1186/s12936-016-1084-1",
language = "English",
volume = "15",
journal = "Malaria Journal",
issn = "1475-2875",
publisher = "BioMed Central",
number = "1",

}

Valecha, N, Savargaonkar, D, Srivastava, B, Rao, BHK, Tripathi, SK, Gogtay, N, Kochar, SK, Kumar, NBV, Rajadhyaksha, GC, Lakhani, JD, Solanki, BB, Jalali, RK, Arora, S, Roy, A, Saha, N, Iyer, SS, Sharma, P & Anvikar, AR 2016, 'Comparison of the safety and efficacy of fixed-dose combination of arterolane maleate and piperaquine phosphate with chloroquine in acute, uncomplicated Plasmodium vivax malaria: A phase III, multicentric, open-label study', Malaria Journal, vol. 15, no. 1, 42. https://doi.org/10.1186/s12936-016-1084-1

Comparison of the safety and efficacy of fixed-dose combination of arterolane maleate and piperaquine phosphate with chloroquine in acute, uncomplicated Plasmodium vivax malaria : A phase III, multicentric, open-label study. / Valecha, Neena; Savargaonkar, Deepali; Srivastava, Bina; Rao, B. H.Krishnamoorthy; Tripathi, Santanu K.; Gogtay, Nithya; Kochar, Sanjay Kumar; Kumar, Nalli Babu Vijaya; Rajadhyaksha, Girish Chandra; Lakhani, Jitendra D.; Solanki, Bhagirath B.; Jalali, Rajinder K.; Arora, Sudershan; Roy, Arjun; Saha, Nilanjan; Iyer, Sunil S.; Sharma, Pradeep; Anvikar, Anupkumar R.

In: Malaria Journal, Vol. 15, No. 1, 42, 27.01.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Comparison of the safety and efficacy of fixed-dose combination of arterolane maleate and piperaquine phosphate with chloroquine in acute, uncomplicated Plasmodium vivax malaria

T2 - A phase III, multicentric, open-label study

AU - Valecha, Neena

AU - Savargaonkar, Deepali

AU - Srivastava, Bina

AU - Rao, B. H.Krishnamoorthy

AU - Tripathi, Santanu K.

AU - Gogtay, Nithya

AU - Kochar, Sanjay Kumar

AU - Kumar, Nalli Babu Vijaya

AU - Rajadhyaksha, Girish Chandra

AU - Lakhani, Jitendra D.

AU - Solanki, Bhagirath B.

AU - Jalali, Rajinder K.

AU - Arora, Sudershan

AU - Roy, Arjun

AU - Saha, Nilanjan

AU - Iyer, Sunil S.

AU - Sharma, Pradeep

AU - Anvikar, Anupkumar R.

PY - 2016/1/27

Y1 - 2016/1/27

N2 - Background: Chloroquine has been the treatment of choice for acute vivax malaria for more than 60 years. Malaria caused by Plasmodium vivax has recently shown resistance to chloroquine in some places. This study compared the efficacy and safety of fixed dose combination (FDC) of arterolane maleate and piperaquine phosphate (PQP) with chloroquine in the treatment of uncomplicated vivax malaria. Methods: Patients aged 13-65 years with confirmed mono-infection of P. vivax along with fever or fever in the previous 48 h were included. The 317 eligible patients were randomly assigned to receive FDC of arterolane maleate and PQP (n = 159) or chloroquine (n = 158) for 3 days. Primaquine was given as an anti-relapse measure on day 3 and continued for 14 consecutive days. Primary efficacy analysis included assessment of the proportion of aparasitaemic and afebrile patients at 72 h. Safety endpoints were analysis of adverse events, vital signs, laboratory data, and abnormalities on electrocardiograph. Patients participated in the study for at least 42 days. Results: In per protocol population, the proportion of aparasitaemic and afebrile patients at 72 h was 100 % (140/140) in the FDC of arterolane maleate and PQP group, and 99.3 % (145/146) in the chloroquine group (Fisher, p > 0.9999). In intent to treat population, the corresponding value was reported to be 96.9 % (154/159) in the FDC of arterolane maleate and PQP group and 98.7 % (156/158) in the chloroquine group (Fisher, p = 0.4479). The median parasite clearance time was 24 h in FDC of arterolane maleate and PQP group and 26 h in chloroquine group (Log-rank, p = 0.2264). Similarly, median fever clearance time was 24 h in both the groups (Log-rank, p = 0.7750). In PP population, day 28 cure rates were 100 % in both the groups (95 % CI (96.52, 100.0 for FDC of arterolane maleate and PQP and 96.73, 100.0 in chloroquine group)). Incidence of adverse events was 82.4 % in the FDC of arterolane maleate and PQP group and 85.4 % in the chloroquine group. Most of the adverse events were mild to moderate in intensity. The commonly reported clinical adverse events in the FDC of arterolane maleate and PQP versus chloroquine group were vomiting (5.0 vs 5.1 %), headache (1.3 vs 3.2 %) and prolonged QT (1.9 vs 3.2 %). No deaths were reported. The pharmacokinetic analysis indicates that arterolane maleate is well absorbed and has a relatively short t1/2 of 3.2 h. Piperaquine is also well absorbed after oral administration with a t1/2 of about 228.33 h. Conclusions: The study showed that FDC of arterolane maleate and PQP effectively cured vivax malaria and attained acceptable level of cure up to day 28. Both the groups showed similar safety profile. Trial Registration Clinical Trial Registry India: CTRI/2011/11/002129.

AB - Background: Chloroquine has been the treatment of choice for acute vivax malaria for more than 60 years. Malaria caused by Plasmodium vivax has recently shown resistance to chloroquine in some places. This study compared the efficacy and safety of fixed dose combination (FDC) of arterolane maleate and piperaquine phosphate (PQP) with chloroquine in the treatment of uncomplicated vivax malaria. Methods: Patients aged 13-65 years with confirmed mono-infection of P. vivax along with fever or fever in the previous 48 h were included. The 317 eligible patients were randomly assigned to receive FDC of arterolane maleate and PQP (n = 159) or chloroquine (n = 158) for 3 days. Primaquine was given as an anti-relapse measure on day 3 and continued for 14 consecutive days. Primary efficacy analysis included assessment of the proportion of aparasitaemic and afebrile patients at 72 h. Safety endpoints were analysis of adverse events, vital signs, laboratory data, and abnormalities on electrocardiograph. Patients participated in the study for at least 42 days. Results: In per protocol population, the proportion of aparasitaemic and afebrile patients at 72 h was 100 % (140/140) in the FDC of arterolane maleate and PQP group, and 99.3 % (145/146) in the chloroquine group (Fisher, p > 0.9999). In intent to treat population, the corresponding value was reported to be 96.9 % (154/159) in the FDC of arterolane maleate and PQP group and 98.7 % (156/158) in the chloroquine group (Fisher, p = 0.4479). The median parasite clearance time was 24 h in FDC of arterolane maleate and PQP group and 26 h in chloroquine group (Log-rank, p = 0.2264). Similarly, median fever clearance time was 24 h in both the groups (Log-rank, p = 0.7750). In PP population, day 28 cure rates were 100 % in both the groups (95 % CI (96.52, 100.0 for FDC of arterolane maleate and PQP and 96.73, 100.0 in chloroquine group)). Incidence of adverse events was 82.4 % in the FDC of arterolane maleate and PQP group and 85.4 % in the chloroquine group. Most of the adverse events were mild to moderate in intensity. The commonly reported clinical adverse events in the FDC of arterolane maleate and PQP versus chloroquine group were vomiting (5.0 vs 5.1 %), headache (1.3 vs 3.2 %) and prolonged QT (1.9 vs 3.2 %). No deaths were reported. The pharmacokinetic analysis indicates that arterolane maleate is well absorbed and has a relatively short t1/2 of 3.2 h. Piperaquine is also well absorbed after oral administration with a t1/2 of about 228.33 h. Conclusions: The study showed that FDC of arterolane maleate and PQP effectively cured vivax malaria and attained acceptable level of cure up to day 28. Both the groups showed similar safety profile. Trial Registration Clinical Trial Registry India: CTRI/2011/11/002129.

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U2 - 10.1186/s12936-016-1084-1

DO - 10.1186/s12936-016-1084-1

M3 - Article

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JO - Malaria Journal

JF - Malaria Journal

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