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Completed

NCT Number: NCT04268784

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

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.

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Key information

Conditions

Healthy Volunteers

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Centre for Human Drug Research (CHDR)

Leiden, South Holland, 2333, Netherlands

About this study

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.).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

DNL343

Drug

Single and repeating oral dose(s)

Placebo

Drug

Single and repeating oral dose(s)

Primary outcomes

  1. Incidence and severity of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs

    Time frame: Up to 20 days

  2. PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma

    Time frame: Up to 20 days

  3. 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

    Time frame: Up to 20 days

  4. PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma

    Time frame: Up to 20 days

  5. 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

    Time frame: Up to 20 days

  6. PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma

    Time frame: Up to 20 days

  7. PK parameter: Apparent terminal elimination rate constant (λz) with the respective t½ of DNL343 in plasma

    Time frame: Up to 20 days

Secondary outcomes

  1. PK parameter: The amount of DNL343 excreted in urine from time zero to 48 hours postdose (Ae48)

    Time frame: Up to 20 days

  2. PK parameter: Estimation of renal clearance (CLR)

    Time frame: Up to 20 days

  3. PK parameter: Concentration of DNL343 in cerebrospinal fluid (CSF)

    Time frame: Up to 20 days

  4. 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)

    Time frame: Up to 20 days

  5. The PD of DNL343 in blood as measured by percent reduction in ISR gene expression levels measured by quantitative polymerase chain reaction (qPCR)

    Time frame: Up to 20 days

Sponsors and collaborators

Lead sponsor

Denali Therapeutics Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Feb 13, 2020
Registry last updated
Feb 7, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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