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Safety and Pharmacokinetics Study of DM1157 to Treat Malaria

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ClinicalTrials.gov Identifier: NCT03490162
Recruitment Status : Not yet recruiting
First Posted : April 6, 2018
Last Update Posted : June 15, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
This is a phase 1 trial to evaluate the safety and pharmacokinetics of single and multiple ascending doses and effect of food on the pharmacokinetics of a novel antimalarial drug in healthy adults. The study will enroll 96 healthy volunteers, males and females, aged 18 to 45 years and will consists of 3 parts: Part 1, Single Ascending Dose (SAD); Part 2, Multiple Ascending Dose (MAD); and Part 3, Food Effect. Part 2 and Part 3 may be initiated after a Safety Monitoring Committee (SMC) review and approval of the of Part 1 safety data. Study duration will be 13 months with patient participation duration 14 days for SAD and Food Effect, and 18 days for MAD. The primary objectives of this study are to: 1) assess the safety and tolerability of single doses of DM1157 at levels ranging from 9 mg to 900 mg; 2) assess the safety and tolerability of DM1157 administered as single daily doses for 3 days at levels ranging from 150 mg to 900 mg; 3) assess the safety and tolerability of DM1157 administered with or without food.

Condition or disease Intervention/treatment Phase
Malaria Drug: DM1157 Other: Placebo Phase 1

Detailed Description:
This is a first-in-humans, phase 1, randomized, double-blind, single-site, placebo-controlled study in 96 healthy volunteers, males and females, aged 18 to 45 years inclusive. The study will consists of 3 parts: Part 1, Single Ascending Dose (SAD) - participants will be administered a single dose (ranges from 9 mg to 900 mg) of DM1157 orally after fasting or a matching placebo; Part 2, Multiple Ascending Dose (MAD) - participants will be administered three doses (ranges from 150 mg to 900 mg) of DM1157 orally once daily for three days after fasting or a matching placebo; and Part 3, Food Effect - participants will be administered 300 mg of DM1157 orally with high fat meal or a matching placebo. Part 2 and Part 3 may be initiated after a Safety Monitoring Committee (SMC) review and approval of the of Part 1 safety data. Study duration will be 13 months with patient participation duration 14 days for SAD and Food Effect, and 18 days for MAD. The primary objectives of this study are to: 1) assess the safety and tolerability of single doses of DM1157 at levels ranging from 9 mg to 900 mg; 2) assess the safety and tolerability of DM1157 administered as single daily doses for 3 days at levels ranging from 150 mg to 900 mg; 3) assess the safety and tolerability of DM1157 administered with or without food. The secondary objectives are to: 1) assess the PK of single doses of DM1157 at levels ranging from 9 mg to 900 mg, including dose proportionality; 2) assess the PK of DM1157 administered as single daily doses for 3 days at levels ranging from 150 mg to 900 mg; 3) assess the PK of 300 mg DM1157 administered with or without food, including determination of the presence or absence of a food effect on exposure.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Pharmacokinetics of Single and Multiple Ascending Doses and Effect of Food on the Pharmacokinetics of DM1157 in Healthy Adults
Estimated Study Start Date : June 29, 2018
Estimated Primary Completion Date : June 4, 2019
Estimated Study Completion Date : June 4, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Food Effect
300 mg of DM1157 (2 capsules of 150 mg) orally with high fat diet, n=6, and matching placebo (2 capsules) orally with high fat diet, n=2
Drug: DM1157
DM1157 is a novel anti-malarial drug that is derived from chloroquine. DM1157 maintains the efficacy of chloroquine and has molecular features that overcome resistance to chloroquine.

Other: Placebo
Placebo

Experimental: MAD 1
150 mg of DM1157 (1 capsule) orally daily for three days with 240 ml of water after an overnight fast, n=8, and matching placebo (1 capsule) orally daily for three days with 240 ml of water after an overnight fast, n=2
Drug: DM1157
DM1157 is a novel anti-malarial drug that is derived from chloroquine. DM1157 maintains the efficacy of chloroquine and has molecular features that overcome resistance to chloroquine.

Other: Placebo
Placebo

Experimental: MAD 2
300 mg of DM1157 (2 capsules of 150 mg) orally daily for three days with 240 ml of water after an overnight fast, n=8, and matching placebo (2 capsules) orally daily for three days with 240 ml of water after an overnight fast, n=2
Drug: DM1157
DM1157 is a novel anti-malarial drug that is derived from chloroquine. DM1157 maintains the efficacy of chloroquine and has molecular features that overcome resistance to chloroquine.

Other: Placebo
Placebo

Experimental: MAD 3
600 mg of DM1157 (4 capsules of 150 mg) orally daily for three days with 240 ml of water after an overnight fast, n=8, and matching placebo (4 capsules) orally daily for three days with 240 ml of water after an overnight fast, n=2
Drug: DM1157
DM1157 is a novel anti-malarial drug that is derived from chloroquine. DM1157 maintains the efficacy of chloroquine and has molecular features that overcome resistance to chloroquine.

Other: Placebo
Placebo

Experimental: MAD 4
900 mg of DM1157 (6 capsules of 150 mg) orally daily for three days with 240 ml of water after an overnight fast, n=8, and matching placebo (6 capsules) orally daily for three days with 240 ml of water after an overnight fast, n=2
Drug: DM1157
DM1157 is a novel anti-malarial drug that is derived from chloroquine. DM1157 maintains the efficacy of chloroquine and has molecular features that overcome resistance to chloroquine.

Other: Placebo
Placebo

Experimental: SAD 1
9 mg of DM1157 (1 capsule) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (1 capsule) orally with 240 ml of water after an overnight fast, n=2
Drug: DM1157
DM1157 is a novel anti-malarial drug that is derived from chloroquine. DM1157 maintains the efficacy of chloroquine and has molecular features that overcome resistance to chloroquine.

Other: Placebo
Placebo

Experimental: SAD 2
45 mg of DM1157 (5 capsules of 9 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (5 capsules) orally with 240 ml of water after an overnight fast, n=2
Drug: DM1157
DM1157 is a novel anti-malarial drug that is derived from chloroquine. DM1157 maintains the efficacy of chloroquine and has molecular features that overcome resistance to chloroquine.

Other: Placebo
Placebo

Experimental: SAD 3
150 mg of DM1157 (1capsule) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (1 capsule) orally with 240 ml of water after an overnight fast, n=2
Drug: DM1157
DM1157 is a novel anti-malarial drug that is derived from chloroquine. DM1157 maintains the efficacy of chloroquine and has molecular features that overcome resistance to chloroquine.

Other: Placebo
Placebo

Experimental: SAD 4
300 mg of DM1157 (2 capsules of 150 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (2 capsules) orally with 240 ml of water after an overnight fast, n=2
Drug: DM1157
DM1157 is a novel anti-malarial drug that is derived from chloroquine. DM1157 maintains the efficacy of chloroquine and has molecular features that overcome resistance to chloroquine.

Other: Placebo
Placebo

Experimental: SAD 5
600 mg of DM1157 (4 capsules of 150 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (4 capsules) orally with 240 ml of water after an overnight fast, n=2
Drug: DM1157
DM1157 is a novel anti-malarial drug that is derived from chloroquine. DM1157 maintains the efficacy of chloroquine and has molecular features that overcome resistance to chloroquine.

Other: Placebo
Placebo

Experimental: SAD 6
900 mg of DM1157 (6 capsules of 150 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (6 capsules) orally with 240 ml of water after an overnight fast (n=2)
Drug: DM1157
DM1157 is a novel anti-malarial drug that is derived from chloroquine. DM1157 maintains the efficacy of chloroquine and has molecular features that overcome resistance to chloroquine.

Other: Placebo
Placebo




Primary Outcome Measures :
  1. Changes in blood pressure in 150 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  2. Changes in blood pressure in 150 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  3. Changes in blood pressure in 300 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  4. Changes in blood pressure in 300 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  5. Changes in blood pressure in 45 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  6. Changes in blood pressure in 600 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  7. Changes in blood pressure in 600 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  8. Changes in blood pressure in 9 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  9. Changes in blood pressure in 900 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  10. Changes in blood pressure in 900 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  11. Changes in heart rate in 150 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  12. Changes in heart rate in 150 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  13. Changes in heart rate in 300 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  14. Changes in heart rate in 300 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  15. Changes in heart rate in 45 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  16. Changes in heart rate in 600 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  17. Changes in heart rate in 600 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  18. Changes in heart rate in 9 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  19. Changes in heart rate in 900 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  20. Changes in heart rate in 900 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  21. Changes in heart rate in Food Effect dose [ Time Frame: Day -1 through Day 14 ]
  22. Changes in temperature in 150 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  23. Changes in temperature in 150 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  24. Changes in temperature in 300 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  25. Changes in temperature in 300 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  26. Changes in temperature in 45 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  27. Changes in temperature in 600 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  28. Changes in temperature in 600 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  29. Changes in temperature in 9 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  30. Changes in temperature in 900 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  31. Changes in temperature in 900 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  32. Changes in temperature in Food Effect dose [ Time Frame: Day -1 through Day 14 ]
  33. ECG changes: arrhythmia in a 150 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  34. ECG changes: arrhythmia in a 150 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  35. ECG changes: arrhythmia in a 300 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  36. ECG changes: arrhythmia in a 300 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  37. ECG changes: arrhythmia in a 45 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  38. ECG changes: arrhythmia in a 600 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  39. ECG changes: arrhythmia in a 600 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  40. ECG changes: arrhythmia in a 9 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  41. ECG changes: arrhythmia in a 900 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  42. ECG changes: arrhythmia in a 900 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  43. ECG changes: arrhythmia in Food Effect dose [ Time Frame: Day -1 through Day 14 ]
  44. ECG changes: PR Interval in 150 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  45. ECG changes: PR Interval in 150 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  46. ECG changes: PR Interval in 300 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  47. ECG changes: PR Interval in 300 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  48. ECG changes: PR Interval in 45 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  49. ECG changes: PR Interval in 600 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  50. ECG changes: PR Interval in 600 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  51. ECG changes: PR Interval in 9 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  52. ECG changes: PR Interval in 900 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  53. ECG changes: PR Interval in 900 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  54. ECG changes: PR Interval in Food Effect dose [ Time Frame: Day -1 through Day 14 ]
  55. ECG changes: QTc/QTch in a 150 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  56. ECG changes: QTc/QTch in a 150 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  57. ECG changes: QTc/QTch in a 300 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  58. ECG changes: QTc/QTch in a 300 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  59. ECG changes: QTc/QTch in a 45 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  60. ECG changes: QTc/QTch in a 600 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  61. ECG changes: QTc/QTch in a 600 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  62. ECG changes: QTc/QTch in a 9 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  63. ECG changes: QTc/QTch in a 900 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  64. ECG changes: QTc/QTch in a 900 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  65. ECG changes: QTc/QTch in Food Effect dose [ Time Frame: Day -1 through Day 14 ]
  66. Number of patients who discontinue study drug due to safety reasons in Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  67. Occurrence of laboratory AEs in 150 mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  68. Occurrence of laboratory AEs in 150 mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  69. Occurrence of laboratory AEs in 300 mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  70. Occurrence of laboratory AEs in 300 mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  71. Occurrence of laboratory AEs in 45 mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  72. Occurrence of laboratory AEs in 600 mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  73. Occurrence of laboratory AEs in 600 mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  74. Occurrence of laboratory AEs in 9 mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  75. Occurrence of laboratory AEs in 900 mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  76. Occurrence of laboratory AEs in 900 mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  77. Occurrence of laboratory AEs in Food Effect dose [ Time Frame: Day 1 through Day 14 ]
  78. Occurrence of unsolicited AEs in a 150-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  79. Occurrence of unsolicited AEs in a 150-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  80. Occurrence of unsolicited AEs in a 300-mg dose taken after food ingestion [ Time Frame: Day 1 through Day 14 ]
  81. Occurrence of unsolicited AEs in a 300-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  82. Occurrence of unsolicited AEs in a 300-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  83. Occurrence of unsolicited AEs in a 45-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  84. Occurrence of unsolicited AEs in a 600-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  85. Occurrence of unsolicited AEs in a 600-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  86. Occurrence of unsolicited AEs in a 9-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  87. Occurrence of unsolicited AEs in a 900-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  88. Occurrence of unsolicited AEs in a 900-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  89. Occurrence of unsolicited SAEs in a 150-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  90. Occurrence of unsolicited SAEs in a 150-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  91. Occurrence of unsolicited SAEs in a 300-mg dose taken after food ingestion [ Time Frame: Day 1 through Day 14 ]
  92. Occurrence of unsolicited SAEs in a 300-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  93. Occurrence of unsolicited SAEs in a 300-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  94. Occurrence of unsolicited SAEs in a 45-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  95. Occurrence of unsolicited SAEs in a 600-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  96. Occurrence of unsolicited SAEs in a 600-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  97. Occurrence of unsolicited SAEs in a 9-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  98. Occurrence of unsolicited SAEs in a 900-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  99. Occurrence of unsolicited SAEs in a 900-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]

Secondary Outcome Measures :
  1. Apparent total clearance of the drug from plasma after oral administration (CL/F) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  2. Apparent total clearance of the drug from plasma after oral administration (CL/F) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  3. Apparent total clearance of the drug from plasma after oral administration (CL/F) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  4. Apparent total clearance of the drug from plasma after oral administration (CL/F) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  5. Apparent total clearance of the drug from plasma after oral administration (CL/F) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  6. Apparent total clearance of the drug from plasma after oral administration (CL/F) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  7. Apparent total clearance of the drug from plasma after oral administration (CL/F) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  8. Apparent total clearance of the drug from plasma after oral administration (CL/F) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  9. Apparent total clearance of the drug from plasma after oral administration (CL/F) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  10. Apparent total clearance of the drug from plasma after oral administration (CL/F) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  11. Apparent total clearance of the drug from plasma after oral administration (CL/F) in Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  12. Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  13. Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  14. Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  15. Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  16. Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  17. Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  18. Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  19. Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  20. Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  21. Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  22. Area under the concentration time-curve extrapolated to infinity (AUC0-inf) in Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  23. Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  24. Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  25. Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  26. Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  27. Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  28. Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  29. Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  30. Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  31. Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  32. Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  33. Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  34. Elimination rate constant (Ke) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  35. Elimination rate constant (Ke) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  36. Elimination rate constant (Ke) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  37. Elimination rate constant (Ke) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  38. Elimination rate constant (Ke) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  39. Elimination rate constant (Ke) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  40. Elimination rate constant (Ke) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  41. Elimination rate constant (Ke) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  42. Elimination rate constant (Ke) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  43. Elimination rate constant (Ke) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  44. Elimination rate constant (Ke) in Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  45. Maximum observed concentration (Cmax) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  46. Maximum observed concentration (Cmax) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  47. Maximum observed concentration (Cmax) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  48. Maximum observed concentration (Cmax) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  49. Maximum observed concentration (Cmax) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  50. Maximum observed concentration (Cmax) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  51. Maximum observed concentration (Cmax) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  52. Maximum observed concentration (Cmax) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  53. Maximum observed concentration (Cmax) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  54. Maximum observed concentration (Cmax) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  55. Maximum observed concentration (Cmax) for Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  56. Oral volume of distribution (V/F) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  57. Oral volume of distribution (V/F) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  58. Oral volume of distribution (V/F) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  59. Oral volume of distribution (V/F) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  60. Oral volume of distribution (V/F) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  61. Oral volume of distribution (V/F) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  62. Oral volume of distribution (V/F) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  63. Oral volume of distribution (V/F) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  64. Oral volume of distribution (V/F) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  65. Oral volume of distribution (V/F) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  66. Oral volume of distribution (V/F) in Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  67. Terminal elimination half-life (t½) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  68. Terminal elimination half-life (t½) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  69. Terminal elimination half-life (t½) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  70. Terminal elimination half-life (t½) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  71. Terminal elimination half-life (t½) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  72. Terminal elimination half-life (t½) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  73. Terminal elimination half-life (t½) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  74. Terminal elimination half-life (t½) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  75. Terminal elimination half-life (t½) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  76. Terminal elimination half-life (t½) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  77. Terminal elimination half-life (t½) in Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  78. Time of maximum observed concentration (Tmax) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  79. Time of maximum observed concentration (Tmax) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  80. Time of maximum observed concentration (Tmax) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  81. Time of maximum observed concentration (Tmax) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  82. Time of maximum observed concentration (Tmax) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  83. Time of maximum observed concentration (Tmax) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  84. Time of maximum observed concentration (Tmax) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  85. Time of maximum observed concentration (Tmax) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  86. Time of maximum observed concentration (Tmax) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  87. Time of maximum observed concentration (Tmax) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  88. Time of maximum observed concentration (Tmax) in Food Effect Dose [ Time Frame: Day 1 through Day 6 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Is a healthy male or nonpregnant female age 18 to 45 years, inclusive.
  2. Can understand the informed consent process and procedures.
  3. Agrees to be available for all study visits.
  4. If a woman of childbearing potential*, agrees to use 2 acceptable contraception methods** from 30 days before first study drug administration until 90 days after last study drug administration.

    *Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy, or successful Essure placement (permanent, nonsurgical, nonhormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or less than 1 year of the last menses if menopausal.

    **Includes, but is not limited to, nonmale sexual relationships, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more before the subject receives the first study drug dose, barrier methods such as condoms or diaphragms with spermicide or foam, effective intrauterine devices, NuvaRing, and licensed hormonal methods such as implants, injectables, or oral contraceptives. If sexually active, methods can include condoms, spermicidal gel, diaphragm, hormonal or nonhormonal intrauterine device, surgical sterilization, oral contraceptive pill, and depot progesterone injections.

  5. If male, agrees to use a barrier method of birth control from 30 days before first study drug administration until 90 days after last study drug administration.
  6. Has adequate venous access for blood draws.

Exclusion Criteria:

  1. Any medical disease or condition that, in the opinion of the site PI or appropriate sub investigator, is a contraindication to study participation.
  2. History of clinically significant ECG abnormalities or has clinically significant ECG abnormalities at Screening.
  3. Use of any prescription medication (excluding oral contraceptive pills in females) within 14 days before first study drug administration.
  4. Use of occasional nonprescription drugs* (oral or topical) within 7 days before first study drug administration unless permitted by the investigator.

    *Nonprescription drugs include vitamins, antacids, herbal or dietary supplements, and topical gels, creams, etc., that in the opinion of the site PI could interfere with the study drug.

  5. Hypertension with confirmed systolic blood pressure (BP) greater than 145 mm Hg or confirmed diastolic BP greater than 90 mm Hg, measured after 10 to 15 minutes of rest.
  6. Heart rate (HR) less than 50 bpm or greater than 100 bpm.
  7. Body mass index (BMI) 18 to 35 kg/m^2, inclusive.
  8. Body weight less than 50 kg.
  9. History of a significant illness within 2 weeks before dosing (subjects can screen after illness is resolved for 2 weeks).
  10. History of hemolytic anemia.
  11. History of retinal eye disease.
  12. History of hearing loss.
  13. History of seizures.
  14. History of thyroid disease or currently on replacement therapy for hypothyroidism.
  15. History of severe drug hypersensitivity, including a severe allergic reaction, anaphylaxis, or convulsions following any medication, vaccination, or infusion.
  16. History of malignancy except low-grade skin cancer (ex. basal cell carcinoma thought to be cured).
  17. Known diagnosis of prolonged QT interval, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure.
  18. History of drug or alcohol abuse within 12 months before Screening.
  19. History of renal disease.
  20. Excessive consumption of beverages containing xanthine bases, including Red Bull, chocolate, etc., or more than 400 mg of caffeine per day (more than 4 cups of coffee per day).
  21. Consumption of citrus fruits or juices (ex. pomegranate, orange, lime, grapefruit) within 7 days before first study drug administration.
  22. Use of nicotine-containing products within 30 days before Screening and until completion of study.
  23. Consumption of alcohol within 24 hours of first study drug administration.
  24. Has any condition or disease that might affect drug absorption, distribution, or excretion (ex. gastrectomy, diarrhea).
  25. Positive serology results for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody.
  26. Positive drug screen (cannabinoids, amphetamines, barbiturates, cocaine, opiates*, benzodiazepines, phencyclidine) or positive breathalyzer test for alcohol.

    *Subjects should be notified by phone not to consume any poppy seeds within 24 hours before the Screening blood test to avoid false a positive opioid test result.

  27. History of allergic reaction or intolerance to CQ.
  28. Males with a QTcF greater than 450 ms or females with a QTcF greater than 460 ms (Fridericia's correction) at Screening.
  29. Positive pregnancy test within 24 hours before study drug administration; pregnant or nursing.
  30. Screening laboratory tests, specifically total WBC and platelet count, hemoglobin, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine, which meet Grade 1 or higher toxicity. Safety laboratory tests drawn on Day -1 will serve as baseline. Day -1 safety laboratory tests with a Grade 1 severity will not exclude a subject from participation if assessed as not clinically significant by the PI or designee.
  31. Any specific condition that, in the judgment of the site PI, precludes participation because it could affect subject safety.
  32. Received an experimental agent* within 30 days or 5 half-lives (whichever is longer) before study drug administration.

    *Vaccine, drug, biologic, device, blood product, or medication

  33. Is participating or plans to participate in another clinical study with an interventional agent that will be received during participation in this study.
  34. Has donated more than 500 mL of blood within the last month before Screening.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03490162


Contacts
Contact: Jeffery Talbot Guptill 19196841018 jerrery.guptill@duke.edu

Locations
United States, North Carolina
Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit Not yet recruiting
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03490162     History of Changes
Other Study ID Numbers: 16-0088
HHSN272201500006I
First Posted: April 6, 2018    Key Record Dates
Last Update Posted: June 15, 2018
Last Verified: February 21, 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Anti-Malarial
DM1157
Pharmacokinetics
Safety

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents