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

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ClinicalTrials.gov Identifier: NCT04268784
Recruitment Status : Recruiting
First Posted : February 13, 2020
Last Update Posted : January 20, 2021
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: DNL343 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : February 20, 2020
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2021

Arm Intervention/treatment
Experimental: DNL343
Cohort A: Single-ascending dose; Cohort B: Multiple-ascending doses
Drug: DNL343
Single and repeating oral dose(s)

Placebo Comparator: Placebo
Cohort A: Single-ascending dose; Cohort B: Multiple-ascending doses
Drug: Placebo
Single and repeating oral dose(s)




Primary Outcome Measures :
  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 Outcome Measures :
  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 ]


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04268784


Locations
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Netherlands
Centre for Human Drug Research (CHDR) Recruiting
Leiden, South Holland, Netherlands, 2333
Contact: Project Manager    +31 71 5246 400    maurits.vissers@chdr.nl   
Sponsors and Collaborators
Denali Therapeutics Inc.
Investigators
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Study Director: Richard Tsai, MD Denali Therapeutics Inc.
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Responsible Party: Denali Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT04268784    
Other Study ID Numbers: DNLI-F-0001
2019-004027-21 ( EudraCT Number )
First Posted: February 13, 2020    Key Record Dates
Last Update Posted: January 20, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No