HIVPhase 1SCRUMNCT02569346
Bioequivalence Study of CRushed TriUMeq With or Without Drip Feed Compared to the Whole Tablet
A Phase 1 study testing Triumeq, Triumeq crushed + breakfast and Triumeq crushed + drip feed in people with HIV, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Dolutegravir is an HIV-1 integrase inhibitor which is marketed as a single tablet (Tivicay®) and in a fixed dose combination tablet with abacavir and lamivudine (Triumeq®, referred to as TRI). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV
- What is being tested?
- Triumeq, Triumeq crushed + breakfast and Triumeq crushed + drip feed
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2016to May 2016
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subject is at least 18 and not older than 55 years of age at the day of screening.
- Subject weighs at least 40 kg.
- Subject has a BMI of 18.5-30 kg/m2, extremes included.
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
- Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry, haematology and urinalysis testing within four weeks prior to day 1. Results of biochemistry, haematology and urinalysis testing should be within the laboratory's reference ranges (see Appendix A). If laboratory results are not within the reference ranges, the subject is included based on the Investigator's judgment that the observed deviations are not clinically relevant. This should be clearly recorded.
- Subject has a normal blood pressure and pulse rate, according to the Investigator's judgment.
- Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to day 1.
Who cannot join
- Positive HIV test.
- Positive hepatitis B or C test.
- Positive HLA-B*5701 status (the risk for abacavir hypersensitivity reaction to occur is high for subjects who test positive for the HLA-B*5701 allele).
- Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
- Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
- Inability to understand the nature and extent of the study and the procedures required.
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- Pregnant female (as confirmed by an hCG test performed less than 4 weeks before day 1) or breast-feeding female. Female subjects of childbearing potential without adequate contraception, e.g. hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double barrier methods, or two years post-menopausal. They must agree to take precautions in order to prevent a pregnancy throughout the entire conduct of the study.
- Therapy with any drug (including herbal remedies, multivitamins, magnesium- and calcium-containing supplements, etc.) (for two weeks preceding day 1), except for acetaminophen.
- Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), psychiatric disorders, gastro-intestinal disorders, renal disorders (renal failure determined as an estimated Glomerular Filtration Rate (eGFR) below 50 ml/min (MDRD-based)), hepatic disorders (Child-Pugh B or C), hormonal disorders (especially diabetes mellitus), coagulation disorders.
- History of or current abuse of drugs, alcohol or solvents.
- Gluten free diet.
- Participation in a drug study within 60 days prior to day 1.
- Donation of blood within 60 days prior to day 1.
- Febrile illness within 3 days before day 1.
- Co-worker of Radboud university medical center.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Bioequivalence Study of CRushed TriUMeq With or Without Drip Feed Compared to the Whole Tablet (SCRUM)
Dolutegravir is an HIV-1 integrase inhibitor which is marketed as a single tablet (Tivicay®) and in a fixed dose combination tablet with abacavir and lamivudine (Triumeq®, referred to as TRI). For patients with swallowing difficulties, administration of whole tablets can be problematic and tablets are cut or crushed to ease administration.
Currently there is no information about crushing TRI tablets. Therefore this study will be conducted to investigate whether crushed and suspended TRI and crushed and suspended TRI with drip feed are bioequivalent to taking TRI as a whole.
Read the detailed description
Dolutegravir is an HIV-1 integrase inhibitor which is marketed as a single tablet (Tivicay®) and in a fixed dose combination tablet with abacavir and lamivudine (Triumeq®, referred to as TRI). For patients with swallowing difficulties, administration of whole tablets can be problematic and tablets are cut or crushed to ease administration. In addition, if HIV patients develop opportunistic infections, patients can become severely ill and may end up on the intensive care. Patients at the intensive care might not be able to swallow medication. Therefore it is useful to know if it is possible to administer TRI through a different route, like a feeding tube. If TRI can be crushed or dissolved and given through a catheter it is also useful to know if it can be given with drip feed.
Currently there is no information about crushing TRI tablets. Depending on the biopharmaceutical characteristics of a drug formulation, crushing tablets can lead to altered pharmacokinetics of drugs. This has been shown for some of the antiretroviral drugs, such as ritonavir, lopinavir, efavirenz and tenofovir.
It is important to know whether pharmacokinetics are influenced by crushing of tablets as low concentrations are associated with virologic failure. Therefore higher doses or switching to other HIV-drugs might be needed. In addition, higher Cmax and/or exposure can lead to toxicity. As a result therapeutic drug monitoring is advised, or crushing the drug is a contra-indication based on the available data.
It has been shown that DTG plasma concentration is influenced by food, with higher AUC en Cmax after a high-fat meal compared to administration in a fasted state. During clinical development, however, dolutegravir intake was studied without regard to food intake. Therefore, it is recommended that dolutegravir can be taken with or without food.
In addition, it has been shown that simultaneous oral ingestion of antacids and dolutegravir gives a decrease in Cmax and AUC of dolutegravir. This interaction is not shown for co-ingestion with omeprazole, which makes it unlikely that this interaction is caused by a pH-lowering effect influencing the absorption of dolutegravir. It is probably a local gastrointestinal complexation phenomenon, similar to what has been observed with other HIV integrase inhibitors. A possible pharmacokinetic interaction between dolutegravir and complexation formers may be expected. Especially considering the active binding sites of dolutegravir which bind magnesium metal ion cofactors. It is currently unclear if certain foods or liquids containing high amounts of magnesium or other cations, like drip feed, can cause this same interaction.
Therefore this study will be conducted to investigate whether crushed and suspended TRI and crushed and suspended TRI with drip feed are bioequivalent to taking TRI as a whole.
- Conditions
- HIV
- Being tested
- Triumeq, Triumeq crushed + breakfast, Triumeq crushed + drip feed
- Keywords
- Triumeq, Pharmacokinetics, Crushing, Drip feed
- Medical subject headings
- Pressure Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TriumeqDrug
Single-dose Triumeq as a whole tablet
Triumeq crushed + breakfastDrug
Single-dose crushed and suspended tablet of Triumeq
Triumeq crushed + drip feedDrug
Drip feed followed by single-dose crushed and suspended tablet of Triumeq
| Study group | Role | What they receive |
|---|---|---|
| Triumeq whole | Active comparator | Single-dose Triumeq as a whole tablet in a fasted state Receives: Drug: Triumeq crushed + breakfast; Drug: Triumeq crushed + drip feed |
| Triumeq crushed + breakfast | Experimental | Single-dose crushed and suspended Triumeq in a fasted state Receives: Drug: Triumeq; Drug: Triumeq crushed + drip feed |
| Triumeq crushed + drip feed | Experimental | 250 ml drip feed (Nutrison) followed by a single-dose crushed and suspended Triumeq Receives: Drug: Triumeq; Drug: Triumeq crushed + breakfast |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC
Measured: up to 48 hours after administration
Secondary outcomes (1)
Adverse events
Measured: during the entire conduct of the study, 6 weeks in total
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2015 (estimated)
- Study startMar 2016
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02569346
- Sponsor's protocol ID
- UMCN-AKF 15.02
- Acronym
- SCRUM
- Status last verified
- Dec 2020
- First submitted
- 30 Sep 2015
- Last updated
- 7 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Roskam-Kwint M, Bollen P, Colbers A, Duisenberg-van Essenberg M, Harbers V, Burger D. Crushing of dolutegravir fixed-dose combination tablets increases dolutegravir exposure. J Antimicrob Chemother. 2018 Sep 1;73(9):2430-2434. doi: 10.1093/jac/dky191.
PubMed 29796595
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bioequivalence Study of CRushed TriUMeq With or Without Drip Feed Compared to the Whole Tablet (SCRUM)
- ClinicalTrials.gov ID
- NCT02569346
- Acronym / sponsor ID
- SCRUM / UMCN-AKF 15.02
- Conditions
- HIV
- Keywords
- Triumeq, Pharmacokinetics, Crushing, Drip feed
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Mar 2016
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 6 Oct 2015 (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.
Dolutegravir is an HIV-1 integrase inhibitor which is marketed as a single tablet (Tivicay®) and in a fixed dose combination tablet with abacavir and lamivudine (Triumeq®, referred to as TRI). For patients with swallowing difficulties, administration of whole tablets can be problematic and tablets are cut or crushed to ease administration.
Currently there is no information about crushing TRI tablets. Therefore this study will be conducted to investigate whether crushed and suspended TRI and crushed and suspended TRI with drip feed are bioequivalent to taking TRI as a whole.
Detailed description
Dolutegravir is an HIV-1 integrase inhibitor which is marketed as a single tablet (Tivicay®) and in a fixed dose combination tablet with abacavir and lamivudine (Triumeq®, referred to as TRI). For patients with swallowing difficulties, administration of whole tablets can be problematic and tablets are cut or crushed to ease administration. In addition, if HIV patients develop opportunistic infections, patients can become severely ill and may end up on the intensive care. Patients at the intensive care might not be able to swallow medication. Therefore it is useful to know if it is possible to administer TRI through a different route, like a feeding tube. If TRI can be crushed or dissolved and given through a catheter it is also useful to know if it can be given with drip feed.
Currently there is no information about crushing TRI tablets. Depending on the biopharmaceutical characteristics of a drug formulation, crushing tablets can lead to altered pharmacokinetics of drugs. This has been shown for some of the antiretroviral drugs, such as ritonavir, lopinavir, efavirenz and tenofovir.
It is important to know whether pharmacokinetics are influenced by crushing of tablets as low concentrations are associated with virologic failure. Therefore higher doses or switching to other HIV-drugs might be needed. In addition, higher Cmax and/or exposure can lead to toxicity. As a result therapeutic drug monitoring is advised, or crushing the drug is a contra-indication based on the available data.
It has been shown that DTG plasma concentration is influenced by food, with higher AUC en Cmax after a high-fat meal compared to administration in a fasted state. During clinical development, however, dolutegravir intake was studied without regard to food intake. Therefore, it is recommended that dolutegravir can be taken with or without food.
In addition, it has been shown that simultaneous oral ingestion of antacids and dolutegravir gives a decrease in Cmax and AUC of dolutegravir. This interaction is not shown for co-ingestion with omeprazole, which makes it unlikely that this interaction is caused by a pH-lowering effect influencing the absorption of dolutegravir. It is probably a local gastrointestinal complexation phenomenon, similar to what has been observed with other HIV integrase inhibitors. A possible pharmacokinetic interaction between dolutegravir and complexation formers may be expected. Especially considering the active binding sites of dolutegravir which bind magnesium metal ion cofactors. It is currently unclear if certain foods or liquids containing high amounts of magnesium or other cations, like drip feed, can cause this same interaction.
Therefore this study will be conducted to investigate whether crushed and suspended TRI and crushed and suspended TRI with drip feed are bioequivalent to taking TRI as a whole.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Triumeq whole | Active comparator | Drug: Triumeq crushed + breakfast, Drug: Triumeq crushed + drip feedSingle-dose Triumeq as a whole tablet in a fasted state |
| Triumeq crushed + breakfast | Experimental | Drug: Triumeq, Drug: Triumeq crushed + drip feedSingle-dose crushed and suspended Triumeq in a fasted state |
| Triumeq crushed + drip feed | Experimental | Drug: Triumeq, Drug: Triumeq crushed + breakfast250 ml drip feed (Nutrison) followed by a single-dose crushed and suspended Triumeq |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Subject is at least 18 and not older than 55 years of age at the day of screening.
- Subject weighs at least 40 kg.
- Subject has a BMI of 18.5-30 kg/m2, extremes included.
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
- Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry, haematology and urinalysis testing within four weeks prior to day 1. Results of biochemistry, haematology and urinalysis testing should be within the laboratory's reference ranges (see Appendix A). If laboratory results are not within the reference ranges, the subject is included based on the Investigator's judgment that the observed deviations are not clinically relevant. This should be clearly recorded.
Key exclusion criteria (15 listed)
- Positive HIV test.
- Positive hepatitis B or C test.
- Positive HLA-B*5701 status (the risk for abacavir hypersensitivity reaction to occur is high for subjects who test positive for the HLA-B*5701 allele).
- Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
- Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
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 |
|---|---|---|
| TriumeqSingle-dose Triumeq as a whole tablet | Drug | Triumeq crushed + breakfast, Triumeq crushed + drip feed |
| Triumeq crushed + breakfastSingle-dose crushed and suspended tablet of Triumeq | Drug | Triumeq crushed + drip feed, Triumeq whole |
| Triumeq crushed + drip feedDrip feed followed by single-dose crushed and suspended tablet of Triumeq | Drug | Triumeq crushed + breakfast, Triumeq whole |
Primary outcome
AUC
Time frame: up to 48 hours after administration
1 secondary outcome
Adverse events
Time frame: during the entire conduct of the study, 6 weeks in total
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 Dec 2020.
- Results publication: PubMed 29796595Roskam-Kwint M, Bollen P, Colbers A, Duisenberg-van Essenberg M, Harbers V, Burger D. Crushing of dolutegravir fixed-dose combination tablets increases dolutegravir exposure. J Antimicrob Chemother. 2018 Sep 1;73(9):2430-2434. doi: 10.1093/jac/dky191.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Triumeq, Triumeq crushed + breakfast and Triumeq crushed + drip feed in people with HIV, run by Radboud University Medical Center at 1 site in Netherlands.
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 7 inclusion and 15 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 Dec 2020. 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 Netherlands. 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?
AUC (time frame: up to 48 hours after administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02569346, which also lists 1 linked publication.
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 Dec 2020.