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

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: Placebo; Drug: DNL343

• Registration Number: NCT04268784
• Lead Sponsor: Denali Therapeutics Inc.

Brief 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.

Detailed 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.).

Study Timeline

• Study First Submitted: 2020-02-10
• Study First Submitted QC: 2020-02-11
• Study First Posted: 2020-02-13
• Study Start: 2020-02-20
• Primary Completion: 2021-08-03
• Study Completion: 2021-08-03
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-03
• Last Update Posted: 2022-02-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 96

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Cohort A: Single-ascending dose; Cohort B: Multiple-ascending doses
DNL343	DNL343	Cohort A: Single-ascending dose; Cohort B: Multiple-ascending doses

Primary Outcome Measures

Name	Time	Method
Incidence and severity of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs	Up to 20 days
PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma	Up to 20 days
PK parameter: Apparent terminal elimination rate constant (λz) with the respective t½ of DNL343 in plasma	Up to 20 days
PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma	Up to 20 days
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
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-τ) of DNL343 in plasma	Up to 20 days
PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma	Up to 20 days

Secondary Outcome Measures

Name	Time	Method
PK parameter: Concentration of DNL343 in cerebrospinal fluid (CSF)	Up to 20 days
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
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
PK parameter: The amount of DNL343 excreted in urine from time zero to 48 hours postdose (Ae48)	Up to 20 days
PK parameter: Estimation of renal clearance (CLR)	Up to 20 days

Trial Locations

Locations (1)

Centre for Human Drug Research (CHDR); 🇳🇱 Leiden, South Holland, Netherlands