A study in healthy volunteers to compare the test medicine as both a tablet and capsule, to determine the correlation between increases in doses of the test medicine and the amount of test medicine taken up by the body, and to estimate how food affects the test medicine when given as a tablet
| ISRCTN | ISRCTN14438276 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14438276 |
| EudraCT/CTIS number | 2021-005215-31 |
| IRAS number | 1004383 |
| Secondary identifying numbers | BP43130, IRAS 1004383 |
- Submission date
- 26/04/2022
- Registration date
- 24/05/2022
- Last edited
- 30/05/2022
- 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 new recipes of the test medicine, RO7486967, to potentially treat diseases such as inflammatory bowel disease, respiratory diseases including chronic obstructive pulmonary disease and severe asthma and Parkinson’s disease. These diseases are linked by a type of inflammation caused by a protein called NLRP3. The test medicine (RO7486967) is anticipated to reduce this inflammation by specifically targeting and blocking NLRP3 from being activated. This two-part healthy volunteer study is testing up to three different recipes of the test medicine, and how they are affected when taken with food. The frequency of adverse events and how the recipes of the test medicine are tolerated will also be investigated. Results from Part 1 will determine if Part 2a or Part 2b is selected.
Who can participate?
Healthy male and non-pregnant, non-lactating female volunteers aged 18 to 55 years
What does the study involve?
In Part 1 and Part 2a, the test medicine will be given on three occasions and in Part 2b on four occasions. In all parts, volunteers will all receive the same recipes of the test medicine, but in a different order; the order will be assigned by chance. Volunteers will receive an oral dose of a new recipe of the test medicine in the fed or fasted state. In Part 1 and Part 2b, volunteers will also receive the test medicine that will be compared with the other recipes in the fasted state. Volunteers will be discharged from the clinic 48 hours later and there will be a break of at least 7 days in between each dosing occasion. Volunteers will be discharged 48 hours after their final dose and will return to the clinic for a follow-up visit 14 to 21 days later. Volunteer’s blood and urine will be collected throughout the study for analysis of the test medicine and for their safety. Volunteers are expected to be involved in this study for about 10 weeks for Part 1 and 11 weeks for Part 2, from screening to the follow-up visit.
What are the possible benefits and risks of participating?
This is a healthy volunteer study. Participants will be administered RO7486967 only for research purposes and it is not intended that the participants will receive any benefit from it. However, the information learned in this study may help future patients. Participants will be compensated for taking part in this research study with an inconvenience allowance. As this is a Phase I study, the most relevant population is healthy volunteers. It is considered that the risk/benefit evaluation in this study supports the use of healthy volunteers. Non-clinical studies have not revealed any reproductive hazards, however as there is no clinical data on pregnant women available, female participants will be required to follow the contraception requirements. Only healthy male and non-pregnant and non-lactating female participants, aged 18 to 55 years are considered suitable for this study. There is always a risk that the stipend in healthy volunteer studies could represent coercion. The time spent in the clinic, travel, inconvenience and other expenses factor in calculating the stipend. Perception of risk is not considered in this calculation. When investigating new medicines there is always a risk of unexpected side effects and occasionally allergic reactions. Volunteers will be closely monitored during the study. Volunteers may experience side effects from the test medicine in this study. Full information on possible side effects is provided to volunteers in the Participant Information Sheet/Informed Consent Forms. There will be an extended period of fasting for the volunteers taking part in this study. To ensure an adequate fluid intake, the volunteers will be allowed to drink water freely and will be monitored for signs of dehydration and fatigue. Blood samples will be collected during the study. Collection of these samples can cause soreness and bruising of the arms but these problems usually clear up within a few days to a few weeks. ECG stickers on volunteers' chests and limbs may cause some local irritation and may be uncomfortable to remove but volunteers will be closely monitored to ensure any local irritation does not persist. As the test medicine is central nervous system (CNS) acting and may have an effect on volunteers' mental health, so they will be required to complete a questionnaire at regular intervals during the study. The questionnaire assesses an individual's mood and mental wellbeing and will be performed by an appropriately trained physician.
Where is the study run from?
Roche (Switzerland)
When is the study starting and how long is it expected to run for?
April 2022 to September 2022
Who is funding the study?
Roche (Switzerland)
Who is the main contact?
global-roche-genentech-trials@gene.com
Contact information
Scientific
Grenzacherstrasse 124
Basel
4070
Switzerland
| Phone | +41 (0)616881111 |
|---|---|
| global-roche-genentech-trials@gene.com |
Public
Grenzacherstrasse 124
Basel
4070
Switzerland
| Phone | +41 (0)616881111 |
|---|---|
| global-roche-genentech-trials@gene.com |
Principal Investigator
Mere Way
Ruddington Fields
Nottingham
NG11 6JS
United Kingdom
| Phone | +44 (0)3303031000 |
|---|---|
| recruitment@weneedyou.co.uk |
Study information
| Study design | Open randomized controlled cross over trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Other |
| Study type | Other |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A two-part, open-label, randomised, cross-over study to compare new tablet formulations of RO7486967 to the capsule formulation, to perform a preliminary dose proportionality assessment and to estimate the effect of food on the pharmacokinetics of the tablet formulations in healthy participants |
| Study acronym | QSC205468 |
| Study objectives | Parts 1 and 2: 1. To determine the pharmacokinetics (what the body does to the test medicine, PK) of RO7486967 in plasma following administration of single oral doses of RO7486967 in the fasted and fed states. 2. To assess the effect of food on the plasma concentration versus time profiles of RO7486967 and RO7428130 (breakdown product) after a single oral dose of RO7486967 as a tablet formulation. Parts 1 and 2b only: 1. To compare the plasma concentration versus time profiles of RO7486967 and RO7428130 after a single oral dose of 200 mg RO7486967 as a tablet formulation and a capsule formulation. Part 2 only: 1. To compare the plasma concentration-time profiles of RO7486967 and RO7428130 after a single oral dose of 25 mg RO7486967 as a tablet formulation to a single oral dose of 200 mg RO7486967 as a tablet formulation. Parts 1 and 2: 1. To assess the safety and tolerability profiles of the RO7486967 capsule and tablet formulations. |
| Ethics approval(s) | Approval pending, Fast Track REC (Health Research Authority, 2 Redman Place, Stratford, London, E20 1JQ, UK), ref: 22/FT/0053 |
| Health condition(s) or problem(s) studied | Inflammatory bowel disease (IBD), respiratory diseases including chronic obstructive pulmonary disease (COPD) and severe asthma, and Parkinson’s disease |
| Intervention | Part 1: Participants will be randomised to receive a single dose of each of reference Hard Capsules RO7486967 200 mg (2 x 100 mg) in the fasted state, RO7486967 Immediate Release Tablet, 200 mg in the fasted state, and RO7486967 Immediate Release Tablet, 200 mg in the fed state, across three periods. Either option Part 2a or 2b will be chosen based on the results of Part 1. Part 2a: Participants will be randomised to receive a single dose of each of RO7486967 Immediate Release Tablet, 200 mg in the fasted state, RO7486967 Immediate Release Tablet, 25 mg in the fasted state and RO7486967 Immediate Release Tablet, 25 mg in the fed state, across three periods. Part 2b: Participants will be randomised to receive a single dose of each reference Hard Capsules RO7486967 200 mg (2 x 100 mg) in the fasted state, RO7486967 Modified Release Tablet, 200 mg in the fasted state, and RO7486967 Modified Release Tablet, 200 mg in the fed state and RO7486967 Modified Release Tablet, 25 mg in the fasted state, across four periods. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | RO7486967 |
| Primary outcome measure | Parts 1 and 2: 1. Pharmacokinetic (PK) parameters, including (but not limited to) Tmax, Cmax, AUC(0-last), AUC(0-inf), lambda-z and T1/2 for RO7486967 in plasma, as applicable, measured using blood samples at pre-dose and at multiple time points, up to 16 hours post-dose on Day 1, and thereafter on Days 2 and 3. 2. Assessment of food effect on plasma PK parameters Cmax, AUC(0-last) and AUC(0-inf) for RO7486967 and RO7428130, as applicable, in the fed state (test regimens) compared to the fasted state (reference regimens), for RO7486967 in plasma measured using blood samples at pre-dose and at multiple time points, up to 16 hours post-dose on Day 1, and thereafter on Days 2 and 3. Part 1 and Part 2b only: 1. Relative bioavailability of plasma PK parameters Cmax, AUC(0-last) and AUC(0-inf) for RO7486967 and RO7428130, as applicable, for tablet formulations (test regimens) compared to a capsule formulation (reference regimen), in plasma measured using blood samples at pre-dose and at multiple time points, up to 16 hours post-dose on Day 1, and thereafter on Days 2 and 3. Part 2 only: 1. Dose proportionality of plasma PK parameters Cmax, AUC(0-last) and AUC(0-inf) for RO7486967 and RO7428130, as applicable, in the chosen 25 mg RO7486967 tablet formulation (test regimen) compared to the chosen 200 mg RO7486967 tablet formulation (reference regimen), in plasma measured using blood samples at pre-dose and at multiple time points, up to 16 hours post-dose on Day 1, and thereafter on Days 2 and 3. |
| Secondary outcome measures | Parts 1 and 2: 1. Additional safety and tolerability information for RO7486967 collected by assessing the incidence of adverse events (AEs), and change from baseline for Columbia-Suicide Severity Rating Scale (C-SSRS), vital signs, electrocardiograms (ECGs), and laboratory safety tests, from the time of signing the informed consent form to up to 21 days post-final dose (approximately 11 weeks) |
| Overall study start date | 20/04/2022 |
| Completion date | 21/09/2022 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 31 |
| Key inclusion criteria | 1. Healthy males or non-pregnant, non-lactating healthy females 2. Aged 18 to 55 years inclusive at the time of signing the informed consent 3. Body mass index (BMI) of 18.0 to 30.0 kg/m², inclusive, as measured at screening 4. Participants must be willing and able to communicate and participate in the whole study and comply with study requirements 5. Participants must provide written informed consent 6. Participants must agree to adhere to the contraception requirements defined in the clinical protocol |
| Key exclusion criteria | 1. Participants who have received any IMP in a clinical research study within the 90 days prior to the planned first dose date of this study (i.e., Day 1 of Period 1), or less than 5 elimination half-lives prior to Day 1 of Period 1, whichever is longer. Participants who are enrolled and dosed in Part 1 are permitted to be enrolled in Part 2, only if there is a minimum of 90 days washout between the final dose of RO7486967 in Part 1 and the first dose of RO7486967 in Part 2. 2. Participants who are, or are immediate family members of, a study site or sponsor employee. 3. Positive test for SARS-CoV-2 within 30 days prior to Day 1 of Period 1 or evidence of recent SARS-CoV-2 symptomatic infection within the last 3 months. Participants who had asymptomatic, incidental, positive findings can be included if tested more than 30 days prior to screening and test negative at screening and prior to admission to the clinical unit. 4. Fever (body temperature >38°C) or symptomatic viral or bacterial infection within 2 weeks prior to screening. 5. History of any drug or alcohol abuse in the past 2 years. 6. Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 ml glass of wine, depending on type) 7. A confirmed positive alcohol breath test at screening or admission. 8. Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission. 9. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months. 10. Females who are pregnant or lactating (all female participants must have a negative highly sensitive serum [screening] and urine [admission] pregnancy test). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration ≥40 IU/l). Female subjects who are currently receiving HRT and have a serum FSH concentration <40 IU/l may be enrolled at the discretion of the investigator. 11. Male participants with pregnant or lactating partners 12. Participants who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening 13. Clinically significant abnormal clinical chemistry, haematology, coagulation (screening only) or urinalysis as judged by the investigator. Note: Participants with Gilbert’s Syndrome are not allowed. 14. ALP, AST, ALT, total bilirubin or GGT >ULN, INR >1.5 or albumin <34 g/l at screening. Repeat testing (one repeat test at screening and one repeat test at admission) is acceptable for out of range values following approval by the investigator or delegate. 15. Confirmed positive drugs of abuse test result. 16. Positive QuantiFERON test at the screening visit or within 2 months prior to screening. 17. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results. 18. Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <70 mL/min using the Cockcroft-Gault equation 19. Abnormal ECG findings at screening and pre-dose that are considered by the investigator to be clinically significant, e.g. 19.1. QTc interval (QTcF >450 msec) 19.2. Notable resting bradycardia (heart rate [HR] <40 bpm) 19.3. Notable resting tachycardia (HR >100 bpm) 19.4. Evidence of atrial fibrillation, atrial flutter, right or left bundle branch block, Wolf-Parkinson-White Syndrome, or cardiac pacemaker 19.5. Any other significant abnormality 20. Personal or family history of congenital long QT syndrome or sudden death 21. Prior or ongoing medical conditions, medical history, physical findings, or laboratory abnormality that, in the investigator’s (or delegate’s) opinion, could adversely affect the safety of the participant 22. Presence of any underlying physical or psychological medical condition that, in the opinion of the investigator, would make it unlikely that the participant will comply with the protocol or complete the study per protocol 23. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal (GI) disease, neurological or psychiatric disorder, or cirrhosis, as judged by the investigator 24. History of malignancy except for non-melanoma skin cancer excised more than 2 years ago and Cervical intra-epithelial neoplasia that had been successfully cured more than 5 years prior to screening Please see the clinical protocol for further exclusion criteria. |
| Date of first enrolment | 26/05/2022 |
| Date of final enrolment | 21/09/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Ruddington Fields
Nottingham
NG11 6JS
United Kingdom
Sponsor information
Industry
Grenzacherstrasse 124
Basel
4070
Switzerland
| Phone | +41 (0)6168 81111 |
|---|---|
| global-roche-genentech-trials@gene.com | |
| Website | http://www.roche.ch/en/index.htm |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- F. Hoffmann-La Roche Ltd, F. Hoffmann-La Roche & Co, F. Hoffmann-La Roche AG, Roche Holding AG, Roche Holding Ltd, Roche Holding, Roche Holding A.G., Roche Holding, Limited, F. Hoffmann-La Roche & Co.
- Location
- Switzerland
Results and Publications
| Intention to publish date | 21/09/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | 1. Internal report 2. Submission to regulatory authorities The findings of this Phase I study will be shared with the Sponsor, F. Hoffmann-La Roche Ltd., only. As these findings are confidential due to commercial sensitivity, it is not appropriate to share the results of this study with other researchers at this time. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to participant-level data not being a regulatory requirement. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 26/07/2023 | No | No |
Editorial Notes
30/05/2022: ISRCTN received notification of combined HRA/MHRA approval for this trial on 28/05/2022.
26/04/2022: Trial's existence confirmed by the HRA.
