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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02223871




Registration number
NCT02223871
Ethics application status
Date submitted
21/08/2014
Date registered
22/08/2014
Date last updated
22/08/2019

Titles & IDs
Public title
Effect of ACT-451840 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Subjects
Scientific title
A Proof-of-concept Study to Assess the Effect of ACT-451840 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Subjects
Secondary ID [1] 0 0
AC-071-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Subjects 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ACT-451840:
Other interventions - Plasmodium falciparum-infected human erythrocytes:
Treatment: Drugs - Artemether 20 mg and lumefantrine 120mg combination tablet:
Treatment: Drugs - Primaquine:

Experimental: ACT-451840 500 mg - All the participants were infected with Plasmodium falciparum parasites (malaria) using malaria-infected human erythrocytes. When the parasitemia reached 1000 counts/mL, all the participants received 500 mg of ACT-451840 as a single oral dose. Compulsory commencement of treatment with Riamet® (artemether-lumefantrine) to ensure complete clearance of any gametocytes, occurred 16 days after ACT-451840 administration (or earlier if required) for all participants. Primaquine was to be administered as a single dose only in participants for whom gametocytes were still identified after administration of Riamet® rescue medication


Treatment: Drugs: ACT-451840:
ACT-451840 500 mg was provided in 100 mL amber glass bottles formulated as a powder for oral suspension. The ACT-451840 suspension was prepared extemporaneously by addition of 25 mL of water and administered orally under fed condition.

Other interventions: Plasmodium falciparum-infected human erythrocytes:
Each participant was inoculated on Day 0 with approximately 1,800 viable Plasmodium falciparum-infected human erythrocytes administered intravenously.

Treatment: Drugs: Artemether 20 mg and lumefantrine 120mg combination tablet:
Rescue treatment to ensure clearance of Plasmodium falciparum comprising six doses of four tablets (total course of 24 tablets) given over a period of 60 hours. Each dose of tablets administered orally was immediately followed by food or drinks rich in fat (e.g., milk).

Treatment: Drugs: Primaquine:
Rescue treatment to ensure clearance of Plasmodium falciparum, to be taken as a single oral 45 mg dose with food only if gametocytes were identified after administration of Riamet® rescue medication.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Drug-specific Parasite Reduction Ratio (PRR48) of ACT-451840 Over 48 Hours Using a Standardized Approach
Timepoint [1] 0 0
48 hours after study drug administration
Secondary outcome [1] 0 0
Maximum Plasma Concentration (Cmax) of ACT-451840
Timepoint [1] 0 0
From pre-dose to 144 hours after study drug adminsitration
Secondary outcome [2] 0 0
Time to Reach Maximum Plasma Concentration (Tmax) of ACT-451840
Timepoint [2] 0 0
From pre-dose to144 hours after study drug administration
Secondary outcome [3] 0 0
Areas Under the Plasma Concentration-time Curve of ACT-451840
Timepoint [3] 0 0
From pre-dose to144 hours after study drug administration
Secondary outcome [4] 0 0
Terminal Half-life [t(1/2)]
Timepoint [4] 0 0
From pre-dose to144 hours after study drug adminsitration
Secondary outcome [5] 0 0
Change From Baseline in Blood Pressure to End of Study (EOS)
Timepoint [5] 0 0
Day 28 (EOS)
Secondary outcome [6] 0 0
Change From Baseline in Body Temperature up to End of Study (EOS)
Timepoint [6] 0 0
Day 28 (EOS)
Secondary outcome [7] 0 0
Change From Baseline in Respiratory Rate to End of Study (EOS)
Timepoint [7] 0 0
Day 28 (EOS)

Eligibility
Key inclusion criteria
- Body weight, minimum 50 kg, body mass index 18-32 kg/m^2.

- Certified healthy by detailed medical history and physical examination.

- Normal vital signs.

- Normal standard 12-lead electrocardiograph (ECG).

- Laboratory parameters within normal range, unless the investigator considered an
abnormality to be clinically irrelevant.

- Use a double barrier method of contraception (male condom plus diaphragm or plus
intrauterine device or plus hormonal contraceptive by female partner) for at least 14
days prior to the first dose of study drug until 90 days after the last dose.

- Written informed consent prior to undertaking any study procedure.
Minimum age
18 Years
Maximum age
50 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Any history of malaria.

- Traveled to or lived (>2 weeks) in a malaria-endemic country in the past 12 months or
planned travel to a malaria-endemic country during the course of the study.

- Evidence of increased cardiovascular disease risk.

- History of splenectomy.

- Presence or history of drug hypersensitivity, or allergic disease diagnosed and
treated by a physician or history of a severe allergic reaction, anaphylaxis or
convulsions following any vaccination or infusion.

- Presence of current or suspected serious chronic disease.

- Receiving psychiatric drugs or hospitalized within the past 5 years prior to
enrollment for psychiatric illness, history of suicide attempt or confinement for
danger to self or others.

- Frequent headaches and/or migraine, recurrent nausea, and/or vomiting.

- Known inherited genetic anomaly.

- Presence of acute infectious disease or fever within the 5 days prior to study product
administration.

- Evidence of acute illness within 4 weeks prior to screening.

- Significant intercurrent disease.

- Clinically significant disease or condition that might affect drug absorption,
distribution or excretion.

- Any investigational product study within the 12 weeks preceding the study.

- Participation in a research study involving blood sampling greater than 450 mL/ unit
of blood, or blood donation to a blood bank during the 8 weeks preceding the reference
drug dose in the study.

- Subject unwilling to defer blood donations for 6 months.

- Blood donation within 1 month before inclusion.

- Medical requirement for intravenous immunoglobulin or blood transfusions.

- Previous blood transfusion.

- Symptomatic postural hypotension.

- History or presence of alcohol consumption of more than 40 g per day or drug
habituation, or any prior intravenous usage of an illicit substance.

- Smoking more than 5 cigarettes or equivalent per day, unable to stop smoking during
the study.

- Ingestion of poppy seeds within 24 hours of the screening blood test.

- Excessive consumption of beverages containing xanthine bases.

- Any medication within 14 days before inclusion or within 5 times the elimination
half-life of the medication, vaccination within the last 28 days.

- Corticosteroids, anti-inflammatory drugs, immunomodulators or anticoagulants.

- Recent or current therapy with an antibiotic or drug with potential antimalarial
activity.

- Subject who, in the judgment of the investigator, was likely to be non-compliant, or
unable to cooperate because of a language problem or poor mental development; was in
the exclusion period of a previous study; lived alone; who could not be contacted in
case of emergency; who was directly involved in conducting the study; who had no good
peripheral venous access.

- Positive result on any of the following tests: hepatitis B surface antigen,
anti-hepatitis B core antibodies, anti-hepatitis C virus antibodies, anti-human
immunodeficiency virus 1 and 2 antibodies.

- Amphetamine, methamphetamines, barbiturates, benzodiazepines, cocaine, methadone,
opiates, phencyclidine, tetrahydrocannabinols, tricyclic antidepressants detected in
the urine drug screen unless there was an explanation acceptable to the medical
investigator.

- Positive alcohol test.

- Pre-existing prolongation of the interval from beginning of the Q wave until end of
the T wave corrected according to Bazett's formula (QTcB interval ) and considered
clinically significant.

- Family history of sudden death, congenital prolongation of QTc interval, known
congenital prolongation of QTc interval, or any clinical condition known to prolong
the QTc interval. History of symptomatic cardiac arrhythmias or clinically relevant
bradycardia. Electrolyte disturbances.

- ECG abnormalities at screening which in the opinion of the investigator is clinically
relevant or will interfere with the ECG analysis.

- History of clinically significant ECG abnormalities.

- Known hypersensitivity to ACT-451840 or any of its excipients or artemether or other
artemisinin derivatives, lumefantrine or other aryl aminoalcohols.

- Unwillingness to abstain from consumption of citrus fruits or their juices, as well as
all fruit juices from admission to the end of the confinement period.

- Any history or presence of lactose intolerance.

- Ingestion of any drug since the recruitment interview (other than the doses
administered in this study) which, in the opinion of the investigator, could
compromise the study.

- Ingestion of any drug in the week prior to dosing or during the blood sampling period
which, in the opinion of the investigator, could compromise the study.

- Failure to conform to the requirements of the protocol.

- Detection of any drug listed in the protocol in the urine drug screen unless there was
an explanation acceptable to the investigator.

- Vital signs outside the reference range and clinically significant.

Study design
Purpose of the study
Other
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2014
Sample size
Target
Accrual to date
Final
8
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Q-Pharm Clinics - Herston
Recruitment postcode(s) [1] 0 0
4006 - Herston

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Idorsia Pharmaceuticals Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This was a single-center study using induced blood stage malaria infection to characterize
the activity of ACT-451840 against early Plasmodium falciparum blood stage infection
Trial website
https://clinicaltrials.gov/ct2/show/NCT02223871
Trial related presentations / publications
Marquart L, Baker M, O'Rourke P, McCarthy JS. Evaluating the pharmacodynamic effect of antimalarial drugs in clinical trials by quantitative PCR. Antimicrob Agents Chemother. 2015 Jul;59(7):4249-59. doi: 10.1128/AAC.04942-14. Epub 2015 May 11.
Public notes

Contacts
Principal investigator
Name 0 0
Michelle Lee
Address 0 0
Actelion
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02223871