A study of the effect of BIIB122/DNL151 on midazolam in healthy participants
| ISRCTN | ISRCTN77591825 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN77591825 |
| EudraCT/CTIS number | 2021-002708-10 |
| IRAS number | 303787 |
| ClinicalTrials.gov number | NIl known |
| Secondary identifying numbers | DNLI-C-0008 |
- Submission date
- 01/04/2024
- Registration date
- 15/04/2024
- Last edited
- 09/05/2024
- 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 BIIB122/DNL151 on the pharmacokinetics (PK) of oral MDZ and the safety and tolerability of BIIB122/DNL151 when administered alone and along with a single dose of 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 - 50 years old
What does the study involve?
The total duration of each participant’s involvement in the study will be approximately 7 weeks. At Visit 1, potential participants will be screened; at Visit 2, participants will be confined in a clinical research unit for 13 days; at Visit 3, participants will have an outpatient visit at the clinical research unit.
What are the possible benefits and risks of participating?
Healthy volunteers will not receive any health benefit from participating in the study. The risks of participation are primarily those associated with adverse reactions to the study treatments and procedures; the risks of DNL151 treatment are based on extensive evaluation of 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 of BIIB122/DNL151.
Where is the study run from?
Denali Therapeutics (USA)
When is the study starting and how long is it expected to run for?
July 2021 to November 2021
Who is funding the study?
Denali Therapeutics (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 | A fixed sequence crossover 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 the contact details to request a patient information sheet. |
| Scientific title | A drug-dr interaction study of the effect of BIIB122/DNL151 on midazolam pharmacokinetics in healthy participants |
| Study hypothesis | To assess the pharmacokinetics (PK) of midazolam (MDZ) in the presence and absence of BIIB122/DNL151 |
| Ethics approval(s) |
Approved 13/09/2021, Wales Research Ethics Committee 1 (Health and Care Research Wales, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, United Kingdom; +44 (0)2922941119; Wales.REC1@wales.nhs.uk), ref: 21/WA/0261 |
| Condition | Healthy volunteers |
| Intervention | Treatment Period 1: Single oral dose of MDZ Treatment Period 2: Once daily oral dose of BIIB122/DNL151 for 10 consecutive days, coadministered with a single dose of MDZ on the 10th day The total duration of each participant’s involvement in the study will be approximately 7 weeks. At Visit 1, potential participants will be screened; at Visit 2, participants will be confined in a clinical research unit for 13 days; at Visit 3, participants will have an outpatient visit at the clinical research unit. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | BIIB122/DNL151; midazolam (MDZ) |
| Primary outcome measure | BIIB122/DNL151 and MDZ 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) 4. AUC during a dosage interval (tau) (AUCτ) [Timeframe: Multiple timepoints over 15 days] |
| Secondary outcome measures | 1. BIIB122/DNL151 and MDZ PK parameters, as measured by laboratory analysis of plasma concentrations from blood samples, including, but not limited to, the following: 1.1. Time to maximum concentration (tmax) 1.2. Terminal elimination half-life (t1/2) [Timeframe: Multiple timepoints over 15 days] 2.Safety assessment including: 2.1. Incidence of treatment-emergent adverse events (TEAEs) and SAEs as reported by the participant [Timeframe: Continuously over 15 days] 2.2. Laboratory assessments of blood and urine samples (including hematology, serum clinical chemistry, and urinalysis) [Timeframe: Multiple timepoints over 15 days] 2.3. 12-lead electrocardiograms (ECGs) [Timeframe: Multiple timepoints over 15 days] 2.4. Vital sign abnormalities [Timeframe: Multiple timepoints over 15 days] 2.5. Physical examinations [Timeframe: Multiple timepoints over 15 days] 2.6. Suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) [Timeframe: Multiple timepoints over 15 days] |
| Overall study start date | 22/07/2021 |
| Overall study end date | 19/11/2021 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 50 Years |
| Sex | Both |
| Target number of participants | 16 |
| Total final enrolment | 14 |
| Participant inclusion criteria | 1. Healthy female participants of non-childbearing potential or healthy male participants between 18 and 50 years of age, inclusive 2. Body mass index (BMI) between 18.5 and 31.0 kg/m² and a body weight of at least 50 kg |
| Participant exclusion criteria | 1. Take any concomitant medication at the time of screening or during the study, unless deemed acceptable by the investigator (or designee) and Sponsor 2. Any history of hepatic, pulmonary, and/or renal disease 3. History of serious adverse reaction or serious hypersensitivity to any drug 4. History of allergy to any component of the study intervention 5. Have any surgical or medical condition affecting drug absorption (eg, gastrectomy) |
| Recruitment start date | 27/09/2021 |
| Recruitment end date | 04/11/2021 |
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 | 19/04/2024 |
|---|---|
| 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 | 19/04/2024 | 22/04/2024 | No | No |
Additional files
Editorial Notes
09/05/2024: A public contact was added.
22/04/2024: The basic results have been uploaded as an additional file.
02/04/2024: Trial's existence confirmed by Wales Research Ethics Committee 1.
