A drug-drug interaction study of DNL343 on midazolam in healthy participants
| ISRCTN | ISRCTN26840121 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN26840121 |
| EudraCT/CTIS number | 2022-003926-38 |
| IRAS number | 1007175 |
| Secondary identifying numbers | IRAS 1007175 |
- Submission date
- 12/04/2023
- Registration date
- 21/04/2023
- Last edited
- 07/06/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English Summary
Background and Study Aims
This is a drug-drug interaction (DDI) study to investigate the effect of DNL343 on the pharmacokinetics (PK) of oral midazolam (MDZ). A DDI study is conducted to see how the 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 to 65 years.
What does the Study Involve?
The total duration of each participant’s involvement in the study will be approximately 53 days from screening through follow-up.
What are the Possible Benefits and Risks of Participating?
Healthy volunteers will not receive any health benefit (beyond that of an assessment of their medical status) from participating in the study. The risks of participation are primarily those associated with adverse reactions to the study interventions and procedures. DNL343 has been extensively evaluated in nonclinical studies (ie, animal studies and studies done with cells in a petri dish) and evaluation in clinical studies to characterize its safety profile.
Where is the study run from?
Denali Therapeutics Inc. (USA)
When is the study starting and how long is it expected to run for?
November 2022 to June 2023
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 | Fixed sequence crossover drug-drug interaction study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Pharmaceutical testing facility |
| Study type | Other |
| Participant information sheet | Not available in web format |
| Scientific title | A drug-drug interaction study of the effect of DNL343 on midazolam pharmacokinetics in healthy participants |
| Study hypothesis | To assess the pharmacokinetics (PK) of midazolam (MDZ) in the presence and absence of DNL343 |
| Ethics approval(s) | 1. Approved 10/03/2023, Wales Research Ethics Committee 2 (Health and Care Research Wales, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, UK; +44 (0)2922941119; Wales.REC2@wales.nhs.uk), ref: 23/WA/0041 2. Approved 14/03/2023, MHRA (10 South Colonnade, Canary Wharf, London, E14 4PU, UK; +44 (0)20 3080 6000; info@mhra.gov.uk), ref: CTA 50398/0011/001-0001 The HRA approved the deferral of the publication of trial details. Full details were added after the deferral ended. |
| Condition | Healthy volunteers |
| Intervention | Treatment Period 1: Single oral dose of MDZ Treatment Period 2: Once daily oral dose of DNL343 for 14 days then coadministered with a single dose of MDZ on the 14th day |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | DNL343, midazolam (MDZ) |
| Primary outcome measure | MDZ PK parameters, as measured by laboratory analysis of plasma concentrations from blood samples including, but not limited to, the following at multiple timepoints over 25 days: 1. Maximum concentration (Cmax) 2. Time to reach maximum concentration (tmax) 3. Area under the concentration-time curve from time zero to infinity (AUC∞) 4. Terminal elimination half-life (t1/2) |
| Secondary outcome measures | 1. Incidence of treatment-emergent adverse events (TEAEs) and SAEs as reported by the participant continuously over 25 days: 2. MDZ metabolite PK parameters, as measured by laboratory analysis of plasma concentrations from blood samples including, but not limited to, the following at multiple timepoints over 25 days: 2.1 Maximum concentration (Cmax) 2.2 Time to reach maximum concentration (tmax) 2.3 Area under the concentration-time curve from time zero to infinity (AUC∞) 2.4 Terminal elimination half-life (t1/2) 3. DNL343 PK parameters, as measured by laboratory analysis of plasma concentrations from blood samples including, but not limited to, the following at multiple timepoints over 25 days: 3.1 AUC during a dosage interval (tau) (AUCτ) 3.2 Maximum concentration at steady state (Cmax,ss) |
| Overall study start date | 30/11/2022 |
| Overall study end date | 09/06/2023 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | 16 |
| Total final enrolment | 16 |
| Participant inclusion criteria | 1. Healthy female participants of non-childbearing potential or healthy male participants between 18 and 65 years of age, inclusive 2. Body mass index (BMI) between 18.5 and 30 kg/m² and a body weight of at least 50 kg |
| Participant exclusion criteria | 1. Any history of hepatic, pulmonary, and/or renal disease 2. History of serious adverse reaction or serious hypersensitivity to any drug 3. History of allergy to any component of the study intervention 4. Have any surgical or medical condition affecting drug absorption (eg, gastrectomy) |
| Recruitment start date | 29/03/2023 |
| Recruitment end date | 15/05/2023 |
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/ |
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 | 10/03/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Results summary posted to 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? |
|---|---|---|---|---|---|
| Basic results | 25/03/2024 | 09/05/2024 | No | No |
Additional files
Editorial Notes
07/06/2024: Total final enrolment added.
04/06/2024: Internal review.
09/05/2024: The basic results have been uploaded as an additional file and a public contact was added.
08/05/2024: The information for which publication was previously deferred has been added to the following fields:
1. The public title was changed from "Phase 1 Clinical Study RD 765.35958" to "A drug-drug interaction study of DNL343 on midazolam in healthy participants".
2. The scientific title was changed from "Phase 1 Clinical Study RD 765.35958" to "A drug-drug interaction study of the effect of DNL343 on midazolam pharmacokinetics in healthy participants".
3. Study hypothesis
4. Study design was changed from "Open-label non-randomized pharmacokinetics study in approximately 16 healthy participants" to "Fixed sequence crossover drug-drug interaction study".
5. Interventions
6. Primary outcome measure
7. Secondary outcome measures
8. Participant inclusion criteria
9. Participant exclusion criteria
10. Plain English summary
11. Drug name(s)
12. Study setting
13/04/2023: Trial's existence confirmed by Wales Research Ethics Committee 2.
