A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL343 in Healthy Volunteers

Healthy Volunteers Clinical Trial

Official title:

A Phase 1, Single-Center, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL343 In Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04268784
• Other study ID #: DNLI-F-0001
• Secondary ID: 2019-004027-21
• Status: Completed
• Phase: Phase 1
• Start date: February 20, 2020
• Est. completion date: August 3, 2021

Study information

• Verified date: February 2022
• Source: Denali Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1 study carried out at a single site in 88 healthy male subjects and healthy female subjects of non childbearing potential to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of DNL343.

Description:

This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: August 3, 2021
• Est. primary completion date: August 3, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Key Inclusion Criteria:

• Women of non-childbearing potential and men; aged 18-50 years, inclusive

• BMI 18-32 kg/m², inclusive, and body weight of at least 50 kg

Key Exclusion Criteria:

• History of clinically significant neurologic, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• DNL343
Single and repeating oral dose(s)
• Placebo
Single and repeating oral dose(s)

Locations

Country	Name	City	State
Netherlands	Centre for Human Drug Research (CHDR)	Leiden	South Holland

Sponsors (1)

Lead Sponsor	Collaborator
Denali Therapeutics Inc.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs		Up to 20 days
Primary	PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-8) of DNL343 in plasma		Up to 20 days
Primary	PK parameter: The area under the concentration-time curve from zero to 12 or 24 hours for twice daily (BID) or once daily (QD) dosing, respectively (AUC0-t) of DNL343 in plasma		Up to 20 days
Primary	PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma		Up to 20 days
Primary	PK parameter: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last]) of DNL343 in plasma		Up to 20 days
Primary	PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma		Up to 20 days
Primary	PK parameter: Apparent terminal elimination rate constant (?z) with the respective t½ of DNL343 in plasma		Up to 20 days
Secondary	PK parameter: The amount of DNL343 excreted in urine from time zero to 48 hours postdose (Ae48)		Up to 20 days
Secondary	PK parameter: Estimation of renal clearance (CLR)		Up to 20 days
Secondary	PK parameter: Concentration of DNL343 in cerebrospinal fluid (CSF)		Up to 20 days
Secondary	The PD of DNL343 in blood as measured by percent reduction of integrated stress response (ISR) protein levels measured by enzyme-linked immunosorbent assay (ELISA)		Up to 20 days
Secondary	The PD of DNL343 in blood as measured by percent reduction in ISR gene expression levels measured by quantitative polymerase chain reaction (qPCR)		Up to 20 days