Trial Outcomes & Findings for An Evaluation of Weekly Tafenoquine (NCT NCT02488980)

Last Updated: 2017-05-30

Results Overview

Prophylactic outcome (success/failure) at the end of the prophylactic treatment phase; outcome was based on absence/presence of asexual stage parasites of any Plasmodium species on a single blood smear.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

306 participants

Primary outcome timeframe

24 Weeks

Results posted on

2017-05-30

Participant Flow

This study was conducted at Kombewa Clinic, Kenya. 517 subjects were screened for entry in to the study. 211 of those subjects were not randomized to treatment due either to abnormal lab results, G6PD deficiency, extended QTc interval, failure to clear parasitaemia or "other" reason.

Participant milestones

Participant milestones
Measure	Tafenoquine Tafenoquine 200 mg for three days followed by Tafenoquine 200 once a week for 24 weeks. Tafenoquine: Tafenoquine 200 mg for three days followed by Tafenoquine 200 mg once a week for 24 weeks.	Mefloquine Mefloquine 250 mg for three days followed by Mefloquine 250 once a week for 24 weeks. Mefloquine: Mefloquine 250 mg for three days followed by Mefloquine 250 mg once a week for 24 weeks.	Placebo Placebo Placebo: Placebo for three days followed by placebo once a week for 24 weeks
Overall Study STARTED	104	101	101
Overall Study COMPLETED	102	99	99
Overall Study NOT COMPLETED	2	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Tafenoquine Tafenoquine 200 mg for three days followed by Tafenoquine 200 once a week for 24 weeks. Tafenoquine: Tafenoquine 200 mg for three days followed by Tafenoquine 200 mg once a week for 24 weeks.	Mefloquine Mefloquine 250 mg for three days followed by Mefloquine 250 once a week for 24 weeks. Mefloquine: Mefloquine 250 mg for three days followed by Mefloquine 250 mg once a week for 24 weeks.	Placebo Placebo Placebo: Placebo for three days followed by placebo once a week for 24 weeks
Overall Study Protocol Violation	2	2	2

Baseline Characteristics

An Evaluation of Weekly Tafenoquine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=99 Participants Placebo Placebo: Placebo for three days followed by placebo once a week for 24 weeks	Tafenoquine n=102 Participants Tafenoquine 200 mg for three days followed by Tafenoquine 200 once a week for 24 weeks. Tafenoquine: Tafenoquine 200 mg for three days followed by Tafenoquine 200 mg once a week for 24 weeks.	Mefloquine n=99 Participants Mefloquine 250 mg for three days followed by Mefloquine 250 once a week for 24 weeks. Mefloquine: Mefloquine 250 mg for three days followed by Mefloquine 250 mg once a week for 24 weeks.	Total n=300 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants	5 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	98 Participants n=99 Participants	100 Participants n=107 Participants	97 Participants n=206 Participants	295 Participants n=7 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Sex: Female, Male Female	36 Participants n=99 Participants	36 Participants n=107 Participants	33 Participants n=206 Participants	105 Participants n=7 Participants
Sex: Female, Male Male	63 Participants n=99 Participants	66 Participants n=107 Participants	66 Participants n=206 Participants	195 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	99 Participants n=99 Participants	102 Participants n=107 Participants	99 Participants n=206 Participants	300 Participants n=7 Participants
Race (NIH/OMB) White	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Region of Enrollment Kenya	99 participants n=99 Participants	102 participants n=107 Participants	99 participants n=206 Participants	300 participants n=7 Participants

PRIMARY outcome

Timeframe: 24 Weeks

Outcome measures

Outcome measures
Measure	Placebo n=99 Participants Placebo Placebo: Placebo for three days followed by placebo once a week for 24 weeks	Tafenoquine n=102 Participants Tafenoquine 200 mg for three days followed by Tafenoquine 200 once a week for 24 weeks. Tafenoquine: Tafenoquine 200 mg for three days followed by Tafenoquine 200 mg once a week for 24 weeks.	Mefloquine n=99 Participants Mefloquine 250 mg for three days followed by Mefloquine 250 once a week for 24 weeks. Mefloquine: Mefloquine 250 mg for three days followed by Mefloquine 250 mg once a week for 24 weeks.
Prophylactic Outcome Defined by the Subject Having no Positive Smears Prophylactic Failure	93 participants	90 participants	92 participants
Prophylactic Outcome Defined by the Subject Having no Positive Smears Prophylactic Success (total)	6 participants	12 participants	7 participants
Prophylactic Outcome Defined by the Subject Having no Positive Smears Prophylactic Success (known)	0 participants	6 participants	0 participants
Prophylactic Outcome Defined by the Subject Having no Positive Smears Prophylactic Success (assumed)	6 participants	6 participants	7 participants

SECONDARY outcome

Timeframe: 24 Weeks

Kaplan-Meier survival curves were produced for time to parasitaemia for both first positive smear and two consecutive positive smears. Analysis was based on a calculation of protective efficacy (PE) of tefaenoquine, defined as (1-relative risk of developing parasitaemia tafenoquine: placebo) x100% and 95.5% confidence intervals were constructed for the relative risk using Koopman's method.

Outcome measures

Outcome measures
Measure	Placebo n=99 Participants Placebo Placebo: Placebo for three days followed by placebo once a week for 24 weeks	Tafenoquine n=102 Participants Tafenoquine 200 mg for three days followed by Tafenoquine 200 once a week for 24 weeks. Tafenoquine: Tafenoquine 200 mg for three days followed by Tafenoquine 200 mg once a week for 24 weeks.	Mefloquine n=99 Participants Mefloquine 250 mg for three days followed by Mefloquine 250 once a week for 24 weeks. Mefloquine: Mefloquine 250 mg for three days followed by Mefloquine 250 mg once a week for 24 weeks.
Protective Efficacy Based on Two Consecutive Positive Smears	0 Percentage of Protective Efficacy Interval 0.0 to 0.0	77.9 Percentage of Protective Efficacy Interval 59.7 to 88.2	56.8 Percentage of Protective Efficacy Interval 32.5 to 72.9

SECONDARY outcome

Timeframe: 24 Weeks

Kaplan-Meier survival curves were produced for time to parasitaemia for both first positive smear and two consecutive positive smears. 95.5% confidence intervals were constructed for the relative risk.

Outcome measures

Outcome measures
Measure	Placebo n=99 Participants Placebo Placebo: Placebo for three days followed by placebo once a week for 24 weeks	Tafenoquine n=102 Participants Tafenoquine 200 mg for three days followed by Tafenoquine 200 once a week for 24 weeks. Tafenoquine: Tafenoquine 200 mg for three days followed by Tafenoquine 200 mg once a week for 24 weeks.	Mefloquine n=99 Participants Mefloquine 250 mg for three days followed by Mefloquine 250 once a week for 24 weeks. Mefloquine: Mefloquine 250 mg for three days followed by Mefloquine 250 mg once a week for 24 weeks.
Time to a Single Positive Smear First positive smear	43 Days Interval 42.0 to 50.0	57 Days Interval 53.0 to 70.0	50 Days Interval 44.0 to 64.0
Time to a Single Positive Smear Two consecutive positve smears	63 Days Interval 57.0 to 79.0	0 Days Interval 0.0 to 0.0	165 Days Interval 154.0 to 165.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 weeks

The most commonly reported experiences in subject occurring in at least 20% of subjects in any treatment group.

Outcome measures

Outcome measures
Measure	Placebo n=99 Participants Placebo Placebo: Placebo for three days followed by placebo once a week for 24 weeks	Tafenoquine n=102 Participants Tafenoquine 200 mg for three days followed by Tafenoquine 200 once a week for 24 weeks. Tafenoquine: Tafenoquine 200 mg for three days followed by Tafenoquine 200 mg once a week for 24 weeks.	Mefloquine n=99 Participants Mefloquine 250 mg for three days followed by Mefloquine 250 once a week for 24 weeks. Mefloquine: Mefloquine 250 mg for three days followed by Mefloquine 250 mg once a week for 24 weeks.
Safety (SAEs and AEs) At least one AE	92 participants	98 participants	97 participants
Safety (SAEs and AEs) Headache	37 participants	45 participants	49 participants
Safety (SAEs and AEs) Upper Respiratory Tract Infection	17 participants	30 participants	26 participants
Safety (SAEs and AEs) Back Pain	12 participants	28 participants	10 participants
Safety (SAEs and AEs) Myalgia	25 participants	27 participants	29 participants
Safety (SAEs and AEs) Abdominal Pain	24 participants	25 participants	19 participants
Safety (SAEs and AEs) Coughing	13 participants	24 participants	29 participants
Safety (SAEs and AEs) Rhinitis	21 participants	12 participants	20 participants

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 92 other events

Deaths: 0 deaths

Tafenoquine

Serious events: 10 serious events

Other events: 98 other events

Deaths: 0 deaths

Mefloquine

Serious events: 2 serious events

Other events: 97 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=101 participants at risk Placebo Placebo: Placebo for three days followed by placebo once a week for 24 weeks	Tafenoquine n=104 participants at risk Tafenoquine 200 mg for three days followed by Tafenoquine 200 once a week for 24 weeks. Tafenoquine: Tafenoquine 200 mg for three days followed by Tafenoquine 200 mg once a week for 24 weeks.	Mefloquine n=101 participants at risk Mefloquine 250 mg for three days followed by Mefloquine 250 once a week for 24 weeks. Mefloquine: Mefloquine 250 mg for three days followed by Mefloquine 250 mg once a week for 24 weeks.
Infections and infestations Infection	0.99% 1/101 • Number of events 1 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	1.9% 2/104 • Number of events 2 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Blood and lymphatic system disorders Haemolytic Anaemia	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.96% 1/104 • Number of events 1 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Infections and infestations Cellulitis	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.96% 1/104 • Number of events 1 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Injury, poisoning and procedural complications Injury	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.96% 1/104 • Number of events 1 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Nervous system disorders Headache	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.96% 1/104 • Number of events 1 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Gastrointestinal disorders Enteritis	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.96% 1/104 • Number of events 1 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Reproductive system and breast disorders Unintended pregnancy	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.96% 1/104 • Number of events 1 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Psychiatric disorders Anxiety	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.00% 0/104 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.99% 1/101 • Number of events 1 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Infections and infestations Pneumonia	0.99% 1/101 • Number of events 1 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.96% 1/104 • Number of events 1 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.99% 1/101 • Number of events 1 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Gastrointestinal disorders Moniliasis GI	0.99% 1/101 • Number of events 1 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.00% 0/104 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Respiratory, thoracic and mediastinal disorders Pharyngitis	0.99% 1/101 • Number of events 1 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.00% 0/104 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	0.00% 0/101 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)

Other adverse events

Additional Information

Jose Stoute, MD

Penn State Hershey Infectious Diseases

Phone: 800-243-1455

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=101 participants at risk Placebo Placebo: Placebo for three days followed by placebo once a week for 24 weeks	Tafenoquine n=104 participants at risk Tafenoquine 200 mg for three days followed by Tafenoquine 200 once a week for 24 weeks. Tafenoquine: Tafenoquine 200 mg for three days followed by Tafenoquine 200 mg once a week for 24 weeks.	Mefloquine n=101 participants at risk Mefloquine 250 mg for three days followed by Mefloquine 250 once a week for 24 weeks. Mefloquine: Mefloquine 250 mg for three days followed by Mefloquine 250 mg once a week for 24 weeks.
Nervous system disorders Headache	36.6% 37/101 • Number of events 37 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	43.3% 45/104 • Number of events 45 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	48.5% 49/101 • Number of events 49 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	16.8% 17/101 • Number of events 17 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	28.8% 30/104 • Number of events 30 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	25.7% 26/101 • Number of events 26 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Musculoskeletal and connective tissue disorders Back pain	11.9% 12/101 • Number of events 12 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	26.9% 28/104 • Number of events 28 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	9.9% 10/101 • Number of events 10 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Musculoskeletal and connective tissue disorders Myalgia	24.8% 25/101 • Number of events 25 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	26.0% 27/104 • Number of events 27 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	28.7% 29/101 • Number of events 29 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Gastrointestinal disorders Abdominal pain	23.8% 24/101 • Number of events 24 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	24.0% 25/104 • Number of events 25 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	18.8% 19/101 • Number of events 19 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Respiratory, thoracic and mediastinal disorders Coughing	12.9% 13/101 • Number of events 13 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	23.1% 24/104 • Number of events 24 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	28.7% 29/101 • Number of events 29 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Infections and infestations Infection	19.8% 20/101 • Number of events 20 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	18.3% 19/104 • Number of events 19 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	13.9% 14/101 • Number of events 14 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Injury, poisoning and procedural complications Injury	7.9% 8/101 • Number of events 8 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	17.3% 18/104 • Number of events 18 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	13.9% 14/101 • Number of events 14 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Respiratory, thoracic and mediastinal disorders Pharyngitis	11.9% 12/101 • Number of events 12 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	13.5% 14/104 • Number of events 14 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	13.9% 14/101 • Number of events 14 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Gastrointestinal disorders Gastroenteritis	8.9% 9/101 • Number of events 9 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	12.5% 13/104 • Number of events 13 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	13.9% 14/101 • Number of events 14 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Skin and subcutaneous tissue disorders Pruritus	12.9% 13/101 • Number of events 13 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	12.5% 13/104 • Number of events 13 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	10.9% 11/101 • Number of events 11 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Respiratory, thoracic and mediastinal disorders Rhinitis	20.8% 21/101 • Number of events 21 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	11.5% 12/104 • Number of events 12 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	19.8% 20/101 • Number of events 20 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Nervous system disorders Dizziness	6.9% 7/101 • Number of events 7 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	11.5% 12/104 • Number of events 12 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	13.9% 14/101 • Number of events 14 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Musculoskeletal and connective tissue disorders Arthralgia	7.9% 8/101 • Number of events 8 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	11.5% 12/104 • Number of events 12 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	9.9% 10/101 • Number of events 10 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Infections and infestations Conjunctivitis	12.9% 13/101 • Number of events 13 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	11.5% 12/104 • Number of events 12 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	6.9% 7/101 • Number of events 7 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)
Infections and infestations Viral infection	6.9% 7/101 • Number of events 7 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	4.8% 5/104 • Number of events 5 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)	10.9% 11/101 • Number of events 11 • 28 weeks Subjects with the most frequently reported AEs (\>10 % of subjects in any treatment group)