MalariaPhase 1NCT01205178
G6PD (Glucose-6-phosphate Dehydrogenase) Study to Evaluate Hemolysis Potential of TFQ (Tafenoquine)
A Phase 1 study testing Chloroquine, Primaquine and Tafenoquine in people with Malaria, run by GlaxoSmithKline at 2 sites in Thailand.
Trial summary
SB-252263 (Tafenoquine, TQ) is an 8-aminoquinoline (8-AQ) antimalarial drug being developed by GlaxoSmithKline (GSK), the U.S. Army Medical Research and Materiel Command (USAMRMC) and Medicines for Malaria Venture (MMV). TQ is currently being developed for the radical cure of acute P. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- Chloroquine, Primaquine and Tafenoquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- 2 sitesThailand
- Study dates
- 2 Jul 2009to 1 Apr 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- The subject is between 18 and 45 years of age, inclusive
- A female is eligible to enter and participate in this study if she is non-pregnant, non-lactating and if she is of:
- Non-child bearing potential defined as:
- Is post-menopausal (12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH >40mIU/mL)
- Is pre-menopausal and has had a hysterectomy or a bilateral oophorectomy (removal of the ovaries) or a bilateral tubal ligation with medical report verification.
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- Child-bearing potential, has a negative urine pregnancy test at screening, and agrees to comply with one of the following during the treatment stage of the study and for a period of 90 days after stopping study drug:
- Use of oral contraceptive, either combined or progestogen alone, in combination with a barrier method (e.g., condom or diaphragm)
- Use of an intrauterine device with a documented failure rate of less than 1% per year
- Double barrier method consisting of spermicide with either condom or diaphragm.
- Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female
- Complete abstinence from intercourse for 2 weeks prior to administration of study drug, throughout the study and for a period of 90 days after stopping study drug.
- A signed and dated informed consent is obtained from the subject or the subject's legal representative prior to screening.
- The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned.
- WHO class III G6PD-deficiency or G6PD-normal status must be documented by enzyme activity and cytochemical staining. G6PD genotype must confirm WHO class III G6PD deficiency or G6PD-normal status prior to TQ dosing in all parts of the study (i.e., P. vivax infected subjects may commence CQ therapy whilst the cytochemical staining, enzyme activity and G6PD genotype are being determined).
- Supplemental Inclusion Criteria for Part A: Healthy volunteers Inclusion criteria 1-7 above AND
- Subject is female
- For G6PD-deficient subjects (WHO class III variant), subject must be heterozygous with 40-60% normal RBCs by cytochemical staining method. For G6PD-normal subjects, subject must have >90% normal RBCs by cytochemical staining method.
- Supplemental Inclusion Criteria for Part B: P. vivax patients Inclusion criteria 1-7 above AND
- Subject is female
- Positive blood smear for P. vivax with parasite density >500 and <200,000/µl
- For G6PD-deficient subjects (WHO class III variant), subject must be heterozygous with 40-60% normal RBC by cytochemical staining method. For G6PD-normal subjects, subject must have >90% normal RBCs by cytochemical staining method.
- Supplemental Inclusion Criteria for Part C: P. vivax patients Inclusion criteria 1-7 above AND
- Positive blood smear for P. vivax with parasite density >500 and <200,000/µl
- For G6PD-deficient subjects (WHO class III variant), subject is a homozygous female or a hemizygous male. For G6PD-normal subjects, subject must have >90% normal RBCs by cytochemical staining method
Who cannot join
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- Clinically significant illness (intercurrent illness e.g. pneumonia, pre-existing condition e.g. renal disease, malignancy or conditions that may affect absorption of study medication e.g. severe diarrhea or any signs of malnutrition as defined clinically, and clinical signs and symptoms of vascular disease (e.g. cardiac, CNS, diabetes, hyperlipidemia, etc.).
- Any clinically relevant biological or physical abnormality found or reported at screening which, in the opinion of the investigator, is clinically significant and would preclude safe participation in this study. These abnormalities may be identified on the screening history and physical or laboratory examination, 12-lead electrocardiogram (ECG).
- Mixed malaria infections by Giemsa smear.
- Female subjects who are pregnant, lactating or unwilling/unable to comply with recognized contraceptive methods during the treatment stage of the study and for a period of 90 days after stopping study drug.
- Symptoms of severe vomiting (no food or inability to take food during the previous 8 hours).
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- History of hemoglobinopathy (e.g. sickle-cell disease, hereditary spherocytosis, thalassemias, hemoglobin M, etc.); or current or past history of methemoglobinemia or methemoglobin percentage above 3%.
- History of porphyria
- History of psoriasis
- History of allergy to tafenoquine, chloroquine, primaquine, mefloquine or any other 4- or 8-aminoquinolines.
- Subject has taken other anti-malarials (e.g., mefloquine, primaquine, chloroquine) within the past 60 days by history.
- Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
- Donation of blood in excess of 500mL within 56 days prior to dosing study drug.
- History of regular alcohol consumption exceeding 7 drinks/week for women or 14 drinks/week for men (one drink = five ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months of screening.
- History of illicit drug abuse within 6 months of the study.
- Heparin sensitivity (if heparin is used to maintain intravenous catheter patency).
- QTc interval >450 msec at screening Supplemental Exclusion Criteria for Part A: Healthy volunteers Exclusion criteria 1-16 above AND
- Baseline Hgb <12 g/dL (or Hct <36%). Value to be verified by conducting two measurements (single blood draw).
- Use of prescription or non-prescription drugs, vitamins, herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, or use of St. John's Wort within 28 days prior to the first dose of study medication. Unless in the opinion of the investigator and sponsor the medication will not interfere with study procedures or compromise safety. By exception, the subject may take paracetamol or acetaminophen (≤2 grams/day) up to 48 hours prior to the first dose of study medication.
- Supplemental Exclusion Criteria for Parts B and C: P. vivax patients
- Exclusion criteria 1-16 above AND Laboratory criteria for exclusion are:
- platelets <50,000/µL
- WBC <2000/µL
- Calculated creatinine clearance (CrCl) <50ml/min by Cockcroft-Gault formula:
- Men: CrCl = (140 - age) x weight(kg)/(72 x SCr*)
- Woman: CrCl = [(140 - age) x weight(kg)/(72 x SCr*)] x 0.85
- SCr= serum creatinine
- ALT or AST >2 times upper limit of the reference range
- Total bilirubin level >1.5 times upper limit of the reference range at screening.
- Screening Hgb <11 g/dL (or Hct <33%). Value to be verified by conducting two measurements (single blood draw).
- Subjects who have taken or will likely require the use of medications from the prohibited medication list which include the following classes:
- Histamine-2 blockers and antacids
- Drugs with hemolytic potential
- Drugs known to prolong the QTc interval
Trial locations and contacts
2 sites in 1 country.
Thailand2 sites
GSK Investigational Site
Bangkok, 10700
GSK Investigational Site
Tak, 63110
About this study
Official title: A Phase I Study to Investigate the Hemolytic Potential of Tafenoquine in Healthy Subjects With Glucose-6-phosphate Dehydrogenase Deficiency and the Safety and Tolerability of Tafenoquine in Acute Plasmodium Vivax Malaria Patients With Glucose-6-phosphate Dehydrogenase Deficiency
SB-252263 (Tafenoquine, TQ) is an 8-aminoquinoline (8-AQ) antimalarial drug being developed by GlaxoSmithKline (GSK), the U.S. Army Medical Research and Materiel Command (USAMRMC) and Medicines for Malaria Venture (MMV). TQ is currently being developed for the radical cure of acute P. vivax malaria in combination with standard doses of CQ, which is 1500 mg over 3 days.
The current gold standard for radical cure of P. vivax malaria in many areas of the world is chloroquine (CQ) for clearance of the acute parasitemia immediately followed by primaquine (PQ) to clear the liver stages of the parasite and prevent disease relapse. The 8-AQ class of drugs, including PQ, is hemolytic in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The current study will identify a dose of TQ within the target efficacious dose range that has a hemolytic effect similar to or less than PQ 15 mg OD x 14 days (i.e. ≤ 25-30% hemoglobin decline in WHO class III G6PD-deficient subjects).
- Conditions
- Malaria
- Being tested
- Chloroquine, Primaquine, Tafenoquine
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChloroquineDrug
The current gold standard for radical cure of P. vivax malaria in many areas of the world is chloroquine (CQ); typically 600 mg day 1, 600 mg day 2, 300 mg day 3 for clearance of the acute parasitemia. After this Tafenoquine will be given and subject will be followed up.
PrimaquineDrug
Primaquine (PQ) is another 8 aminoquinoline drug available for Malaria treatment
TafenoquineDrug
Once daily on Day 1 only. For Part B and C of this study Chloroquine will be given to treat Malaria
| Study group | Role | What they receive |
|---|---|---|
| Tafenoquine | Active comparator | Tafenoquine, TQ is an 8-aminoquinoline (8-AQ) antimalarial drug being developed for the radical cure of acute P. vivax malaria. Chloroquine will be given for the first 3 days in second and third part of this study to treat Malaria. Receives: Drug: Chloroquine; Drug: Tafenoquine |
| Chloroquine | Active comparator | Dose for first 3 days for Part B \& C of the study Receives: Drug: Chloroquine |
| Primaquine | Active comparator | once daily for first 14 days Receives: Drug: Primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety, tolerability, and hemolytic potential of TQ in G6PD-deficient female healthy volunteers compared with G6PD-normal female healthy volunteers. This will be done by measuring maximum absolute decline in Haemoglobin from baseline
Measured: 2 years
Secondary outcomes (1)
Maximum absolute decline in Hgb (or Hct) from baseline for TQ in G6PD-deficient healthy volunteers compared to G6PD-normal healthy volunteers.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2010 (estimated)
- Study start2 Jul 2009
- Primary completion1 Apr 2013
- Study completion1 Apr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medicines for Malaria Venture
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01205178
- Sponsor's protocol ID
- 110027
- Status last verified
- Jun 2017
- First submitted
- 18 Mar 2010
- Last updated
- 7 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Investigate the Hemolytic Potential of Tafenoquine in Healthy Subjects With Glucose-6-phosphate Dehydrogenase Deficiency and the Safety and Tolerability of Tafenoquine in Acute Plasmodium Vivax Malaria Patients With Glucose-6-phosphate Dehydrogenase Deficiency
- ClinicalTrials.gov ID
- NCT01205178
- Acronym / sponsor ID
- 110027
- Conditions
- Malaria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Collaborators
- Medicines for Malaria Venture
- Study start
- 2 Jul 2009 (actual)
- Primary completion
- 1 Apr 2013 (actual)
- Study completion
- 1 Apr 2013 (actual)
- First posted
- 20 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
SB-252263 (Tafenoquine, TQ) is an 8-aminoquinoline (8-AQ) antimalarial drug being developed by GlaxoSmithKline (GSK), the U.S. Army Medical Research and Materiel Command (USAMRMC) and Medicines for Malaria Venture (MMV). TQ is currently being developed for the radical cure of acute P. vivax malaria in combination with standard doses of CQ, which is 1500 mg over 3 days.
The current gold standard for radical cure of P. vivax malaria in many areas of the world is chloroquine (CQ) for clearance of the acute parasitemia immediately followed by primaquine (PQ) to clear the liver stages of the parasite and prevent disease relapse. The 8-AQ class of drugs, including PQ, is hemolytic in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The current study will identify a dose of TQ within the target efficacious dose range that has a hemolytic effect similar to or less than PQ 15 mg OD x 14 days (i.e. ≤ 25-30% hemoglobin decline in WHO class III G6PD-deficient subjects).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tafenoquine | Active comparator | Drug: Chloroquine, Drug: TafenoquineTafenoquine, TQ is an 8-aminoquinoline (8-AQ) antimalarial drug being developed for the radical cure of acute P. vivax malaria. Chloroquine will be given for the first 3 days in second and third part of this study to treat Malaria. |
| Chloroquine | Active comparator | Drug: ChloroquineDose for first 3 days for Part B \& C of the study |
| Primaquine | Active comparator | Drug: Primaquineonce daily for first 14 days |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (25 listed)
- A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- The subject is between 18 and 45 years of age, inclusive
- A female is eligible to enter and participate in this study if she is non-pregnant, non-lactating and if she is of:
- Non-child bearing potential defined as:
- Is post-menopausal (12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH >40mIU/mL)
Key exclusion criteria (34 listed)
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- Clinically significant illness (intercurrent illness e.g. pneumonia, pre-existing condition e.g. renal disease, malignancy or conditions that may affect absorption of study medication e.g. severe diarrhea or any signs of malnutrition as defined clinically, and clinical signs and symptoms of vascular disease (e.g. cardiac, CNS, diabetes, hyperlipidemia, etc.).
- Any clinically relevant biological or physical abnormality found or reported at screening which, in the opinion of the investigator, is clinically significant and would preclude safe participation in this study. These abnormalities may be identified on the screening history and physical or laboratory examination, 12-lead electrocardiogram (ECG).
- Mixed malaria infections by Giemsa smear.
- Female subjects who are pregnant, lactating or unwilling/unable to comply with recognized contraceptive methods during the treatment stage of the study and for a period of 90 days after stopping study drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChloroquineThe current gold standard for radical cure of P. vivax malaria in many areas of the world is chloroquine (CQ); typically 600 mg day 1, 600 mg day 2, 300 mg day 3 for clearance of the acute parasitemia. After this Tafenoquine will be given and subject will be followed up. | Drug | Chloroquine, Tafenoquine |
| PrimaquinePrimaquine (PQ) is another 8 aminoquinoline drug available for Malaria treatment | Drug | Primaquine |
| TafenoquineOnce daily on Day 1 only. For Part B and C of this study Chloroquine will be given to treat Malaria | Drug | Tafenoquine |
Primary outcome
To evaluate the safety, tolerability, and hemolytic potential of TQ in G6PD-deficient female healthy volunteers compared with G6PD-normal female healthy volunteers. This will be done by measuring maximum absolute decline in Haemoglobin from baseline
Time frame: 2 years
1 secondary outcome
Maximum absolute decline in Hgb (or Hct) from baseline for TQ in G6PD-deficient healthy volunteers compared to G6PD-normal healthy volunteers.
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2017.
- Results for study 110027 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Chloroquine, Primaquine and Tafenoquine in people with Malaria, run by GlaxoSmithKline at 2 sites in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the safety, tolerability, and hemolytic potential of TQ in G6PD-deficient female healthy volunteers compared with G6PD-normal female healthy volunteers. This will be done by measuring maximum absolute decline in Haemoglobin from baseline (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2017.