Novel Regimens of Tafenoquine for Prevention of Malaria in Malaria-Naive Subjects

A method of prevention of symptomatic malaria in a human subject, comprising:

• a) administering to the human subject an initial dose of a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I), one or more times prior to potential exposure of the subject to at least one species of Plasmodium;
• b) administering to the human subject an exposure dose of a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I), one or more times per week during potential exposure of the subject to at least one species of Plasmodium;
• and
• c) administering to the human subject a post-exposure dose of a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I), one or more times after potential exposure of the subject to at least one species of Plasmodium,
• wherein a serum or plasma concentration of at least about 80 ng/mL of Formula (I) is attained prior to potential exposure, maintained during potential exposure, and maintained for at least three weeks after potential exposure of the subject to at least one species of Plasmodium,
• wherein the human subject is malaria-naïve and Glucose-6-phosphate dehydrogenase (G6PD) normal, and
• wherein Formula (I) has the following structure,

A method of prevention of symptomatic malaria in a human subject, comprising:

• a) administering to the human subject an initial dose of a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I), one or more times prior to potential exposure of the subject to at least one species of Plasmodium, wherein each said initial dose is between about 75 and about 299 mg;
• and
• b) administering to the human subject an exposure dose of a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I), one or more times per week during potential exposure of the subject to at least one species of Plasmodium, wherein the total administered amount of the exposure dose is between about 175 and 195 mg per week;
• wherein the human subject is malaria-naïve and Glucose-6-phosphate dehydrogenase (G6PD) normal, and
• wherein Formula (I) has the following structure,

A method of prevention of symptomatic malaria in a human subject, comprising:

• c) administering to the human subject an initial dose of a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I), one or more times prior to potential exposure of the subject to at least one species of Plasmodium, wherein the total pre-exposure dose exceeds about 500 mg;
• and
• d) administering to the human subject an exposure dose of a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I), two or more times per week during potential exposure of the subject to at least one species of Plasmodium, wherein the total administered amount of the exposure dose is at least about 175 mg per week;
• wherein the human subject is malaria-naïve and Glucose-6-phosphate dehydrogenase (G6PD) normal, and
• wherein Formula (I) has the following structure,

A kit comprising:

• a) one or more initial dose(s) of about 40 to about 299 mg of a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I);
• b) multiple exposure doses wherein the total administered amount of the exposure dose is about 75 to 299 mg per week of a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I);
• c) one or more post-exposure dose of about 40 to about 299 mg of a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I);
• and
• d) instructions for taking said initial dose one or more times prior to potential exposure of the subject to at least one species of Plasmodium, taking said exposure dose one or more times per week during potential exposure of the subject to at least one species of Plasmodium, and for taking said post-exposure dose one or more times after potential exposure of the subject to at least one species of Plasmodium,
• wherein Formula (I) has the following structure,

A kit comprising:

• a) one or more primary dose(s) of at least three initial dose(s) of about 40 to about 299 mg of a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I);
• b) one or more post-exposure dose of about 40 to about 299 mg of a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I);
• and
• c) instructions for taking said primary dose one or more times prior to taking said post-exposure dose one or more times after potential exposure of the subject to at least one species of Plasmodium,
• wherein Formula (I) has the following structure,