Trial found no impact of Malarone(TM) on performance and alertness tasks

Results from a new study presented today at the 75th Annual Scientific Meeting of the Aerospace Medical Association (AsMA) in Anchorage, USA, suggest that MalaroneTM (atovaquone and proguanil hydrochloride) would not be expected to affect the ability of pilots and cabin crew to perform their duties while on an aircraft (1). The risk of developing clinical malaria for aircrew flying to highly endemic regions is estimated at 0.5 per 1000 persons per overnight stay (2). Considerable periods of incapacity and fatal cases in aircrew have been reported (3).

The study is the first to assess side effects of an antimalarial drug in a hypobaric chamber at aircraft cabin pressure (75.2kPa), and the results showed that clinically effective levels of MalaroneTM [250mg atovaquone + 100 mg proguanil HCl] were well tolerated and had no significant effect on vigilance, alertness, processing complex information, sleepiness and duration or quality of sleep for the volunteers.

"Use of medication for aircrew on duty is prohibited by national law and international rules, unless convincing evidence can be provided that the treatment in question has no negative effects on performance and alertness. Therefore, we submitted these data to the Civil Aviation Authorities of The Netherlands and the Joint Aviation Authorities of Europe for their consideration to recommend the use of MalaroneTM in pilots and cabin crew," said Dr Ries Simons of the TNO Human Factors Institute, Soesterberg, The Netherlands.

The randomized double-blind cross-over study involved 22 healthy volunteers who received MalaroneTM or placebo for a 14 day period, and underwent rigorous performance testing while in a hypobaric chamber that was pressurized to the minimum pressure for commercial airlines. This included tests developed by NASA to assess performance and alertness tasks similar to activities that aircraft crew members perform in-flight. There were no significant differences between the test results following MalaroneTM or placebo dosing. These results support those from a previous study where, under normal pressure conditions, MalaroneTM had no impact on traditional psychomotor testing, simulating flying performance nor on the subjective assessment of mood, sleepiness, or fatigue (4).

Adverse events were comparable for both study treatment arms, and all were classified as mild, short lasting and most frequently related to GI problems.

Dr Dereck Tait, Director, Clinical Development said: "These new data provide further evidence for the favourable safety profile of MalaroneTM. The safety and tolerability of MalaroneTM have been demonstrated in several clinical trials, and in two of these, conducted in nearly 2000 non-immune subjects, MalaroneTM had fewer drug related adverse events than mefloquine (5) and chloroquine/proguanil (6)."

MalaroneTM should be started 1–2 days before travel and continued daily until 7 days after travel, making it ideal for people who spend only a short period of time in an endemic area, such as aircrew.

MalaroneTM is approved for the prophylaxis and treatment of P. falciparum malaria, the most common and serious type of malaria.

Notes to Editors:

About GSK:
GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information, visit GlaxoSmithKline on the World Wide Web at www.gsk.com

About TNO Human Factors:
TNO HUMAN FACTORS is one of the 15 institutes that constitute the Netherlands Organisation for Applied Scientific Research TNO, a knowledge organisation for companies, government bodies and public organisations. TNO Human Factors mission is to offer innovative solutions that enhance human performance in demanding environments. The Aerospace Medicine department of TNO Human Factors is specialised in research of the effects of medication on flight safety. Methods include performance tests, using tasks relevant for optimal pilot performance, and simulated aircraft cabin environmental conditions. For company information, visit TNO Human Factors on the World Wide Web at www.tm.tno.nl

TNO Human Factor Enquiries:

M. Simons, MD, Research Physician Aviation Medicine
31-346-356-485
simons@tm.tno.nl

GlaxoSmithKline Enquiries:

Chris Hunter-Ward
Corporate Media UK
44-208-047-5502

References:

1 Abstract, presented May 2004, 75th Annual Scientific Meeting of the Aerospace Medical Association (AsMA) in Anchorage, USA
2 Steffen R, Holdener F, Wyss R, Nurminen L. Malaria prophylaxis and self-therapy in airline crews. Aviat Space Environ Med 1990; 61:942-945
3 Simons M. Malaria prophylaxis for aircrew: emphasis on individual measures and education. 4th International Conference on Travel Medicine, Acapulco, Mexico, April 1995
4 Paul MA, McCarthy AE, Gibson N, Kenny G, Cook T, Gray G. The impact of Malarone? and Primaquine on psychomotor performance. Aviat Space Environ Med 2003; 74:738-745
5 Overbosch D, Schilthuis H, Bienzle U, Behrens RH, Kain KC, Clarke PD, Toovey S, Knobloch J, Nothdurft HD, Shaw D, Roskell NS, Chulay JD. Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomized, double blind study. Clin Inf Diseases 2001; 33:1015-1021
6 Hogh B, Clarke PD, Camus D, Nothdurft HD, Overbosch D, Gunther M, Joubert I, Kain KC, Shaw D, Roskell NS, Chulay JD; Malarone International Study Team. Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune traveller: a randomised, double-blind study. Lancet 2000; 356(9245):1888-94

---

---