Drug InteractionNCT05680792
Pharmacokinetic Interaction Between Nitazoxanide and Atazanavir/Ritonavir in Healthy Volunteers
A study testing Nitazoxanide and Atazanavir/ritonavir in people with Drug Interaction, run by Obafemi Awolowo University at 1 site in Nigeria.
Trial summary
The goal of this study is to 1. determine the most effective biological sampling method that best describe the pharmacokinetics nitazoxanide/tizoxanide and to; 2. evaluate the clinical significance of the pharmacokinetics interaction between nitazoxanide (1000mg twice daily) and atazanavir/ritonavir (300mg/100mg). Read more about this study
- Who is it for?
- Ages 18 to 41 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Interaction
- What is being tested?
- Nitazoxanide and Atazanavir/ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteNigeria
- Study dates
- 10 Sep 2020to 31 Jan 2023
- Phase
- Interventional
- 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 41 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- The study population will include both male and female healthy volunteers that are eighteen years or above
- non-smokers, non-alcoholics, had not taken any medication or coffee 2 weeks before participating, were non-pregnant and non-breastfeeding
Who cannot join
- Pregnant women will be excluded from the study. Moreover, volunteers who have been on any other drugs in the last two weeks will also be excluded from the study.
- Exclusion criteria included any sickness or reaction to the study drugs.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Pharmacokinetic Interaction Between Nitazoxanide and Atazanavir/Ritonavir in Healthy Volunteers
The goal of this study is to
- determine the most effective biological sampling method that best describe the pharmacokinetics nitazoxanide/tizoxanide and to;
- evaluate the clinical significance of the pharmacokinetics interaction between nitazoxanide (1000mg twice daily) and atazanavir/ritonavir (300mg/100mg).
Read more
Participants will be given 1000mg oral nitazoxanide taken twice daily for seven days. After a washout period of three weeks, they will receive 1000mg oral nitazoxanide with atazanavir/ritonavir (taken orally at 300/100 mg). Five millimetres of whole blood or swab or saliva samples will be collected from them at 0.5, 1, 2, 4, 6, 8 and 12 hours after dose on day 1, 5 and 7.
The pharmacokinetic of nitazoxanide when administered alone and alongside atazanavir/ritonavir will be compared to see if concomitant administration of nitazoxanide and atazanavir/ritonavir affect nitazoxanide pharmacokinetics
Read the detailed description
Nitazoxanide is an antiprotozoal drug with a well-understood and documented safety profile. It was first approved by the US Food and Drug Administration (FDA) in July 2004 for the treatment of diarrhoea caused by Giardia lamblia or Cryptosporidium parvum in adults (≥ 18 years) and paediatrics (1-17 years). Nitazoxanide has also demonstrated in-vitro anti-SARS-CoV-2 activity. A review of in vitro studies reporting the anti-coronavirus activity of nitazoxanide and its active metabolite, tizoxanide, is available. Nitazoxanide was among the three top inhibitors of coronavirus replication, resulting in a reduction of 6 log10 in virus titer with an IC50 of 1.0 µM. The major circulating metabolite of nitazoxanide is tizoxanide, and it has also been confirmed to have activity against SARS-CoV-216. Both suppress the cytopathic effect of SARS-CoV-2. Nitazoxanide is also active against the influenza A virus and was shown to reduce symptom duration in uncomplicated acute influenza. Since SARS-CoV-2 shares almost 80% of the genome with SARSCoV19 and almost all encoded proteins of SARS-CoV-2 are homologous to SARS-CoV proteins, nitazoxanide and its metabolite tizoxanide with demonstrated activity against SARS-CoV are likely to be effective against SARS-CoV-2. Since the virus replicates quickly, antivirals must remain active across their dosing interval. Therefore, enhanced drug concentration will be needed in the lung throughout the dosing interval.
The HIV protease inhibitor, atazanavir (boosted with ritonavir), has been shown to inhibit the major protease enzyme required for viral polyprotein processing during coronavirus replication. It also blocks pro-inflammatory cytokine production. Similar to nitazoxanide, atazanavir has been shown to achieve effective concentration in the pulmonary tissues at the approved dose of 300 mg in combination with 100 mg of ritonavir, with even more favourable ratios when compared to in vitro activities generated in human cell models.
Therefore, based on these considerations, the combination of nitazoxanide (taken orally at 1000 mg twice daily) and atazanavir/ritonavir (taken orally at 300/100 mg once daily) is being considered for selection for intervention for the treatment of COVID-19. Hence, this study wants to evaluate the clinical usefulness of the combination of these drugs. The approach is to characterise the extent of drug-drug interaction of nitazoxanide and atazanavir/ritonavir when 1000 mg nitazoxanide is taken two times daily in combination with 300/100 mg atazanavir/ritonavir before deploying the combination for the intervention.
- Conditions
- Drug Interaction
- Being tested
- Nitazoxanide, Atazanavir/ritonavir
- Keywords
- Nitazoxanide, atazanavir/ritonavir, drug-drug interaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NitazoxanideDrug
Also called Netazox
1000 mg nitazoxanide tablets twice daily. The drug will be administered after meal for 5 days
Atazanavir/ritonavirDrug
300/100 mg atazanavir/ritonavir tablets in the evening once daily, to be administered after meal for 5 days.
| Study group | Role | What they receive |
|---|---|---|
| Administration of nitazoxanide alone | Other | Participants in this arm will receive 1000 mg of nitazoxanide tablets alone Receives: Drug: Nitazoxanide |
| Administration of nitazoxanide plus atazanavir/ritonavir | Other | Participants in this arm will receive 1000 mg of nitazoxanide tablets twice daily together with one tablet of atazanavir/ritonavir (300 mg/100 mg) once daily in the morning. Receives: Drug: Nitazoxanide; Drug: Atazanavir/ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minimum plasma concentration (Cmin)
Tizoxanide minimum plasma concentration with or without atazanavir/ritonavir
Measured: After the first dose (Day 1)
Minimum plasma concentration (Cmin)
Tizoxanide minimum plasma concentration with or without atazanavir/ritonavir
Measured: At Day 5
Maximum plasma concentration (Cmax)
Tizoxanide maximum plasma concentration with or without atazanavir/ritonavir
Measured: After the first dose (Day 1)
Maximum plasma concentration (Cmax)
Tizoxanide maximum plasma concentration with or without atazanavir/ritonavir
Measured: At Day 5
Area under the concentration-time curve (AUC)
Tizoxanide Area under the concentration-time curve with or without atazanavir/ritonavir
Measured: After the first dose (Day 1)
Area under the concentration-time curve (AUC)
Tizoxanide Area under the concentration-time curve with or without atazanavir/ritonavir
Measured: At Day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2023
- Study start10 Sep 2020
- Primary completion10 Jan 2023
- Study completion31 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug InteractionStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Obafemi Awolowo University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Liverpool
- Responsible party
- Principal investigator, Babatunde Adeagbo, Obafemi Awolowo University
- Investigators
- Babatunde A Adeagbo, PhD, Principal investigator, Obafemi Awolowo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05680792
- Sponsor's protocol ID
- IPH/OAU/12/1574
- Status last verified
- Sep 2023
- First submitted
- 7 Dec 2022
- Last updated
- 13 Sep 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Pharmacokinetic Interaction Between Nitazoxanide and Atazanavir/Ritonavir in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT05680792
- Acronym / sponsor ID
- IPH/OAU/12/1574
- Conditions
- Drug Interaction
- Keywords
- Nitazoxanide, atazanavir/ritonavir, drug-drug interaction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Obafemi Awolowo UniversityUniversity, hospital or other
- Collaborators
- University of Liverpool
- Study start
- 10 Sep 2020 (actual)
- Primary completion
- 10 Jan 2023 (actual)
- Study completion
- 31 Jan 2023 (actual)
- First posted
- 11 Jan 2023 (actual)
- 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.
The goal of this study is to
- determine the most effective biological sampling method that best describe the pharmacokinetics nitazoxanide/tizoxanide and to;
- evaluate the clinical significance of the pharmacokinetics interaction between nitazoxanide (1000mg twice daily) and atazanavir/ritonavir (300mg/100mg).
Participants will be given 1000mg oral nitazoxanide taken twice daily for seven days. After a washout period of three weeks, they will receive 1000mg oral nitazoxanide with atazanavir/ritonavir (taken orally at 300/100 mg). Five millimetres of whole blood or swab or saliva samples will be collected from them at 0.5, 1, 2, 4, 6, 8 and 12 hours after dose on day 1, 5 and 7.
The pharmacokinetic of nitazoxanide when administered alone and alongside atazanavir/ritonavir will be compared to see if concomitant administration of nitazoxanide and atazanavir/ritonavir affect nitazoxanide pharmacokinetics
Detailed description
Nitazoxanide is an antiprotozoal drug with a well-understood and documented safety profile. It was first approved by the US Food and Drug Administration (FDA) in July 2004 for the treatment of diarrhoea caused by Giardia lamblia or Cryptosporidium parvum in adults (≥ 18 years) and paediatrics (1-17 years). Nitazoxanide has also demonstrated in-vitro anti-SARS-CoV-2 activity. A review of in vitro studies reporting the anti-coronavirus activity of nitazoxanide and its active metabolite, tizoxanide, is available. Nitazoxanide was among the three top inhibitors of coronavirus replication, resulting in a reduction of 6 log10 in virus titer with an IC50 of 1.0 µM. The major circulating metabolite of nitazoxanide is tizoxanide, and it has also been confirmed to have activity against SARS-CoV-216. Both suppress the cytopathic effect of SARS-CoV-2. Nitazoxanide is also active against the influenza A virus and was shown to reduce symptom duration in uncomplicated acute influenza. Since SARS-CoV-2 shares almost 80% of the genome with SARSCoV19 and almost all encoded proteins of SARS-CoV-2 are homologous to SARS-CoV proteins, nitazoxanide and its metabolite tizoxanide with demonstrated activity against SARS-CoV are likely to be effective against SARS-CoV-2. Since the virus replicates quickly, antivirals must remain active across their dosing interval. Therefore, enhanced drug concentration will be needed in the lung throughout the dosing interval.
The HIV protease inhibitor, atazanavir (boosted with ritonavir), has been shown to inhibit the major protease enzyme required for viral polyprotein processing during coronavirus replication. It also blocks pro-inflammatory cytokine production. Similar to nitazoxanide, atazanavir has been shown to achieve effective concentration in the pulmonary tissues at the approved dose of 300 mg in combination with 100 mg of ritonavir, with even more favourable ratios when compared to in vitro activities generated in human cell models.
Therefore, based on these considerations, the combination of nitazoxanide (taken orally at 1000 mg twice daily) and atazanavir/ritonavir (taken orally at 300/100 mg once daily) is being considered for selection for intervention for the treatment of COVID-19. Hence, this study wants to evaluate the clinical usefulness of the combination of these drugs. The approach is to characterise the extent of drug-drug interaction of nitazoxanide and atazanavir/ritonavir when 1000 mg nitazoxanide is taken two times daily in combination with 300/100 mg atazanavir/ritonavir before deploying the combination for the intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Administration of nitazoxanide alone | Other | Drug: NitazoxanideParticipants in this arm will receive 1000 mg of nitazoxanide tablets alone |
| Administration of nitazoxanide plus atazanavir/ritonavir | Other | Drug: Nitazoxanide, Drug: Atazanavir/ritonavirParticipants in this arm will receive 1000 mg of nitazoxanide tablets twice daily together with one tablet of atazanavir/ritonavir (300 mg/100 mg) once daily in the morning. |
Who may qualify
- Ages
- 18 to 41 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- The study population will include both male and female healthy volunteers that are eighteen years or above
- non-smokers, non-alcoholics, had not taken any medication or coffee 2 weeks before participating, were non-pregnant and non-breastfeeding
Key exclusion criteria (2 listed)
- Pregnant women will be excluded from the study. Moreover, volunteers who have been on any other drugs in the last two weeks will also be excluded from the study.
- Exclusion criteria included any sickness or reaction to the study drugs.
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 |
|---|---|---|
| NitazoxanideAlso: Netazox1000 mg nitazoxanide tablets twice daily. The drug will be administered after meal for 5 days | Drug | Administration of nitazoxanide alone, Administration of nitazoxanide plus atazanavir/ritonavir |
| Atazanavir/ritonavir300/100 mg atazanavir/ritonavir tablets in the evening once daily, to be administered after meal for 5 days. | Drug | Administration of nitazoxanide plus atazanavir/ritonavir |
Primary outcome
Minimum plasma concentration (Cmin)
Time frame: After the first dose (Day 1)
Tizoxanide minimum plasma concentration with or without atazanavir/ritonavir
Minimum plasma concentration (Cmin)
Time frame: At Day 5
Tizoxanide minimum plasma concentration with or without atazanavir/ritonavir
Maximum plasma concentration (Cmax)
Time frame: After the first dose (Day 1)
Tizoxanide maximum plasma concentration with or without atazanavir/ritonavir
Maximum plasma concentration (Cmax)
Time frame: At Day 5
Tizoxanide maximum plasma concentration with or without atazanavir/ritonavir
Area under the concentration-time curve (AUC)
Time frame: After the first dose (Day 1)
Tizoxanide Area under the concentration-time curve with or without atazanavir/ritonavir
Area under the concentration-time curve (AUC)
Time frame: At Day 5
Tizoxanide Area under the concentration-time curve with or without atazanavir/ritonavir
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 13 Sep 2023.
- Individual participant dataSharing planned: No
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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.
Babatunde A Adeagbo, PhD principal investigator
Obafemi Awolowo University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nitazoxanide and Atazanavir/ritonavir in people with Drug Interaction, run by Obafemi Awolowo University at 1 site in Nigeria.
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 2 inclusion and 2 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 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Nigeria. 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.
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?
Minimum plasma concentration (Cmin) (time frame: After the first dose (Day 1)). The study lists 6 primary outcomes in all. 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 13 Sep 2023.