A study evaluating the effect of itraconazole on DNL343 in healthy participants
| ISRCTN | ISRCTN77943537 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN77943537 |
| EudraCT/CTIS number | 2021-006382-37 |
| IRAS number | 310753 |
| Secondary identifying numbers | DNLI-F-0005, IRAS 310753 |
- Submission date
- 05/03/2024
- Registration date
- 14/03/2024
- Last edited
- 31/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
This is a drug-drug interaction (DDI) study designed to evaluate the pharmacokinetics (PK), safety, and tolerability of a single dose of DNL343 in the absence and presence of itraconazole (ITZ) with a planned enrollment of 16 healthy participants. A DDI study is run to see how two drugs interact in the body; evaluating PK is figuring out how participants' bodies handle a drug or drugs in combination.
Who can participate?
Healthy volunteers aged 18 - 55 years
What does the study involve?
The total duration of each participant’s involvement in the study will be approximately 73 days from screening through follow-up.
What are the possible benefits and risks of participating?
Healthy participants in this study will not receive any health benefit from participating in the study. The risks of DNL343 treatment are based on extensive evaluation in nonclinical studies (ie, animal studies and studies done with cells in a petri dish) and evaluation in clinical studies in healthy participants to characterize the safety profile. The potential risks of participation are primarily those associated with adverse reactions to the study interventions (DNL343 and ITZ).
Where is the study run from?
Denali Therapeutics Inc. (USA)
When is the study starting and how long is it expected to run for?
December 2021 to July 2022
Who is funding the study?
Denali Therapeutics Inc. (USA)
Who is the main contact?
Clinical Trials Disclosures Group at Denali Therapeutics, clinical-trials-disclosures@dnli.com
Contact information
Principal Investigator
Simbec-Orion Clinical Pharmacology
Merthyr Tydfil Industrial Park
Cardiff Road
Merthyr Tydfil
CF48 4DR
United Kingdom
| Phone | +44 (0)1443694315 |
|---|---|
| helen.philpott@simbecorion.com |
Public, Scientific
Simbec-Orion Clinical Pharmacology
Merthyr Tydfil Industrial Park
Cardiff Road
Merthyr Tydfil
CF48 4DR
United Kingdom
| Phone | +44 (0)1443 694319 |
|---|---|
| gabrielle.brill@simbecorion.com |
Public
Denali Therapeutics
-
-
United States of America
| Phone | None provided |
|---|---|
| clinical-trials-disclosures@dnli.com |
Study information
| Study design | Phase 1 single-center open-label fixed-sequence drug-drug interaction study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Other |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A fixed-sequence, drug-drug interaction study evaluating the effect of the cytochrome P450 3A inhibitor itraconazole on DNL343 in healthy participants |
| Study objectives | To evaluate the pharmacokinetics (PK) safety, and tolerability of a single dose of DNL343 in the absence and presence of itraconazole. |
| Ethics approval(s) |
Approved 18/01/2022, Wales Research Ethics Committee 2 (Health and Care Research Wales Castlebridge 4 15-19 Cowbridge Road East, Cardiff, CF11 9AB, United Kingdom; +44 (0)2922941119; Wales.REC2@wales.nhs.uk), ref: 22/WA/0009 |
| Health condition(s) or problem(s) studied | Healthy volunteers |
| Intervention | Single oral dose of DNL343 without and with repeating oral doses of itraconazole. The total duration of each participant’s involvement in the study will be approximately 73 days from screening through follow-up. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | DNL343; itraconazole |
| Primary outcome measure | DNL343 PK parameters, as measured by laboratory analysis of plasma concentrations from blood samples, including, but not limited to, the following: 1. Maximum concentration (Cmax) 2. Area under the concentration-time curve from time zero to infinity (AUC∞) 3. Area under the concentration-time curve from time zero to time of last measurable concentration (AUClast) [Timeframe: Multiple timepoints over 45 days] |
| Secondary outcome measures | Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs) as reported by the participant (or, when appropriate, by a caregiver, a surrogate, or the participant's legally authorized representative) [Timeframe: Continuously over 45 days] |
| Overall study start date | 16/12/2021 |
| Completion date | 25/07/2022 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 55 Years |
| Sex | Both |
| Target number of participants | 16 |
| Total final enrolment | 24 |
| Key inclusion criteria | 1. Healthy male participants and healthy female participants of non-childbearing potential 2. Aged ≥18 to ≤55 years 3. Body mass index (BMI) of ≥18.5 to ≤30 kg/m² 4. Body weight of ≥50 kg |
| Key exclusion criteria | 1. History of clinically significant endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders 2. History of malignancy, except fully resected basal cell carcinoma 3. History of clinically significant neurological or psychiatric diseases 4. History of serious adverse reaction or serious hypersensitivity to any drug, or history of allergy to any component of the DNL343 or itraconazole products 5. Are pregnant (ie, positive pregnancy test) or breastfeeding |
| Date of first enrolment | 09/02/2022 |
| Date of final enrolment | 18/05/2022 |
Locations
Countries of recruitment
- United Kingdom
- Wales
Study participating centre
Cardiff Road
Merthyr Tydfil
CF48 4DR
United Kingdom
Sponsor information
Industry
161 Oyster Point Boulevard
South San Francisco
94080
United States of America
| Phone | +1 (0)650 866 8548 |
|---|---|
| clinical-trials@dnli.com | |
| Website | https://www.denalitherapeutics.com/ |
"ROR" |
https://ror.org/00pprn321 |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- DENALI, Denali Therapeutics Inc.
- Location
- United States of America
Results and Publications
| Intention to publish date | 25/01/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | We intend to request an update to the record with a results summary by the time the results deferral lapses (25Jan2025). |
| 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? |
|---|---|---|---|---|---|
| Basic results | 21/07/2023 | 31/01/2025 | No | No |
Additional files
Editorial Notes
31/01/2025: The basic results have been uploaded as an additional file.
09/05/2024: A public contact was added.
08/04/2024: Internal review.
05/03/2024: Trial's existence confirmed by Wales Research Ethics Committee 2
