A study in healthy volunteers to assess different doses (quantity) of the test medicine (Aprepitant) and to investigate the impact of food on the different doses of the test medicine
| ISRCTN | ISRCTN51392723 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN51392723 |
| IRAS number | 1005687 |
| Secondary identifying numbers | IRAS 1005687, QSC206159 |
- Submission date
- 16/09/2022
- Registration date
- 05/10/2022
- Last edited
- 06/05/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
The sponsor is developing a new recipe of the test medicine, aprepitant, for the potential treatment of cancer. Aprepitant is currently used to treat nausea and vomiting related the chemotherapy, however in preclinical trials it was found to have anticancer effects at higher doses than currently given to patients. This single part, healthy volunteer study will investigate how the test medicine is taken up by the body, safety and tolerability and varying and increasing dose, and the effect of food may be explored.
Who can participate?
Healthy males aged 18 – 55 inclusive.
What does the study involve?
The study consists of one part, involving a single cohort of 12 male volunteers. In each period, volunteers will receive single oral doses of the test medicine. In period 1, volunteers will receive a 150 mg dose of the test medicine, and the results from Period 1 will determine the dose given in Period 2. Period 3 – 5 are optional, and depending on results from the previous period, volunteers may receive a higher dose of the test medicine, or it may be given in the fed state. Volunteers may also receive a dose of the marketed product of aprepitant.
Volunteers will be discharged on Day 3 in each period and will return to the clinical unit on Day 4 of each period for the collection of a PK blood sample and for any new adverse events (AE’s) to be recorded. There will be a break of at least 14 days between each period, to make sure there is no test medicine in the volunteers’ bodies before their next dose.
Volunteers will receive a follow up phone call 5 to 7 days following the final dose.
Volunteer’s blood and urine will be taken throughout the study for analysis of the test medicine and for their safety.
Volunteers are expected to be involved in this study for 16 weeks from screening to the follow up call.
What are the possible risks and benefits of participating?
Participants get no medical benefit from taking part in this study. However, development of a treatment for cancer may benefit the population as a whole. It is considered that the risk/benefit evaluation in this study supports the use of healthy volunteers. Full information on possible side effects is provided to volunteers in the Participant Information Sheet and Informed Consent Form. Volunteers are closely monitored during the study and safety assessments are performed regularly.
Where is the study run from?
Quotient Sciences, Nottingham, UK
When is the study starting and how long is it expected to run for?
August 2022 to February 2023
Who is funding the study?
Oxilio Limited
Who is the main contact?
Simon Yaxley
Simon.yaxley@oxilio.co.uk
Contact information
Principal Investigator
Mere Way
Ruddington Fields
Ruddington
Nottingham
NG11 6JS
United Kingdom
| Phone | +44 (0)330 3031000 |
|---|---|
| recruitment@weneedyou.co.uk |
Public
Danebrook Court
Langford Lane
Kidlington
Oxford
OX5 1LQ
United Kingdom
| info@oxilio.co.uk |
Scientific
Danebrook Court
Langford Lane
Kidlington
Oxford
OX5 1LQ
United Kingdom
| info@oxilio.co.uk |
Study information
| Study design | Single-centre single-part five-period controlled study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Sequential open-labelled |
| Study setting(s) | Pharmaceutical testing facility |
| Study type | Other |
| Participant information sheet | Not available in web format |
| Scientific title | A single-part, five-period, sequential, open-labelled study designed to evaluate the safety and pharmacokinetic profile of varying doses of aprepitant following administration of a lipidic capsule formulation (LipAprep) in healthy subjects |
| Study objectives | The trial will meet the following primary and secondary objectives: Primary objectives - To evaluate the pharmacokinetic (PK) profiles of aprepitant following oral administrations of a lipidic capsule formulation (LipAprep) in healthy subjects - To provide safety and tolerability information for aprepitant following oral administrations of a lipidic capsule formulation (LipAprep) in healthy subjects Secondary objectives - To evaluate the PK profiles of aprepitant following oral administrations of an immediate release (IR) marketed reference formulation in healthy subjects (optional) - To assess the relative bioavailability of the aprepitant lipidic capsule formulations (LipAprep) compared to the IR marketed formulation following oral administration in healthy subjects (optional) - To evaluate the PK profiles of aprepitant following oral administrations of the lipidic capsule formulation (LipAprep) at the same dose in the fed and fasted state in healthy subjects (optional) - To provide additional safety and tolerability information for aprepitant following oral administrations of an IR marketed formulation in healthy subjects (optional) |
| Ethics approval(s) |
Approved 21/09/2022, London Bridge Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)2071048387, 2071048124; londonbridge.rec@hra.nhs.uk), ref: 22/LO/0549 |
| Health condition(s) or problem(s) studied | Cancer |
| Intervention | This study will investigate the PK, safety and tolerability of varying or increasing doses of LipAprep capsule formulation and optionally an immediate release aprepitant formulation. Each participant will receive single oral doses of LipAprep on up to 5 occasions across up to 5 treatment periods. In Period 1, volunteers will receive a 150 mg dose of the test medicine. This will determine the single dose given in Period 2. Periods 3 - 5 are optional; volunteers may be given a higher dose or be dosed with a dose previously administered in the fed state. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Aprepitant IR capsule, 125 mg LipAprep capsule 37.5 mg |
| Primary outcome measure | 1. Evaluate the pharmacokinetic (PK) profiles of LipAprep (aprepitant lipidic capsule formulation) by measurement of PK parameters including but not limited to: Tlag, Tmax, Cmax, Cmax/D, C24, AUC(0-24), AUC(0-24)/D, AUC(0-last), AUC(0-last)/D, lambda-z, T1/2, and statistical assessment of dose proportionality, where applicable 2. To provide safety and tolerability information for LipAprep by assessing: incidence of adverse events (AEs), physical examinations and change from baseline for vital signs, electrocardiograms (ECGs), and laboratory safety tests |
| Secondary outcome measures | 1. Evaluate the PK profiles of aprepitant immediate release (IR) marketed reference formulation by measurement of PK parameters including but not limited to: Tlag, Tmax, Cmax, Cmax/D, C24, AUC(0-24), AUC(0-24)/D, AUC(0-last), AUC(0-last)/D, lambda-z and T1/2, where applicable 2. To assess the relative bioavailability of LipAprep compared to the IR marketed formulation by calculation of relative bioavailability (Frel) for Cmax, AUC(0-24) and AUC(0-last), including statistical assessment of relative bioavailability 3. Evaluate PK profiles of LipAprep at the same dose in the fed and fasted state by measurement of PK parameters including but not limited to: Tlag, Tmax, Cmax, Cmax/D, C24, AUC(0-24), AUC(0-24)/D, AUC(0-last), AUC(0-last)/D, lambda-z, T1/2, and statistical assessment of food effect, where applicable 4. To provide additional safety and tolerability information for aprepitant following oral administrations of an IR marketed formulation by assessment of the incidence of AEs, physical examinations and change from baseline for vital signs, ECGs, and laboratory safety tests |
| Overall study start date | 10/08/2022 |
| Completion date | 20/02/2023 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 55 Years |
| Sex | Male |
| Target number of participants | 12 |
| Total final enrolment | 13 |
| Key inclusion criteria | 1. Must provide written informed consent 2. Must be willing and able to communicate and participate in the whole study 3. Aged 18 – 55 at the time of signing informed consent 4. Must agree to adhere to the contraception requirements defined in the protocol 5. Healthy males, determined by no clinically significant findings on ECG, vital signs or urinalysis 6. Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening 7. Weight ≥50 kg at screening |
| Key exclusion criteria | 1. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients 2. Presence or history of clinically significant allergy requiring treatment. Hay fever is allowed unless it is active. 3. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder 4. Subjects with a history of cholecystectomy or gall stones 5. History or presence of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency 6. Subjects who do not have suitable veins for multiple venepunctures/cannulation 7. Evidence of current SARS-CoV-2 infection or recent infection within 4 weeks of first IMP administration or subjects who have ongoing symptoms attributed to COVID-19 8. Clinically significant abnormal clinical chemistry, haematology or urinalysis. Subjects with Gilbert’s Syndrome are allowed. 9. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or HIV 1 and 2 antibody results 10. Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer 11. Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood 12. Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies in the 14 days before IMP administration 13. History of any drug or alcohol abuse in the past 2 years 14. Regular alcohol consumption >21 units per week 15. A confirmed positive alcohol breath test at screening or admission 16. Current smokers and those who have smoked within the last 12 months 17. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months 18. Confirmed positive drugs of abuse test result, as detailed in the protocol 19. Consumption of a low-fat diet within 2 weeks of first dose 20. Male subjects with pregnant or lactating partners 21. Subjects who are, or are immediate family members of, a study site or sponsor employee 22. Failure to satisfy the investigator of fitness to participate for any other reason |
| Date of first enrolment | 14/10/2022 |
| Date of final enrolment | 20/02/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Ruddington Fields
Nottingham
NG11 6JS
United Kingdom
Sponsor information
Research organisation
3 Danebrook Court
Langford Lane
Kidlington
Oxford
OX5 1LQ
England
United Kingdom
| info@oxilio.co.uk |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 18/07/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | In accordance with the approved HRA deferral, full trial details have now been published in the registry. |
| IPD sharing plan | The datasets generated and/or analysed during the current study are not expected to be made available because of their high commercial sensitivity and the negligible benefit to the public of publication of results of non-therapeutic clinical trials |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
06/05/2025: The information for which publication was previously deferred has been added to the following fields:
1. The public title
2. The scientific title
3. Study hypothesis
4. Ethics approval
5. Study design, including primary and secondary study design
6. Study setting(s)
7. The overall study end date was changed from 18/02/2023 to 20/02/2023.
8. Condition
9. Interventions
10. Pharmaceutical study type(s)
11. Drug/device/biological/vaccine name(s)
12. Primary and secondary outcome measures
13. Participant inclusion and exclusion criteria
14. Lower and upper age limits and units
15. Total final enrolment
16. The recruitment start date was changed from 11/10/2022 to 14/10/2022.
17. The recruitment end date was changed from 18/02/2023 to 20/02/2023.
18. Plain English summary
19. Publication and dissemination plan
28/09/2022: Trial's existence confirmed by MHRA.
23/09/2022: The HRA has confirmed deferral has been approved.
