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A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL151 in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04557800
Recruitment Status : Completed
First Posted : September 22, 2020
Last Update Posted : March 7, 2022
Sponsor:
Information provided by (Responsible Party):
Denali Therapeutics Inc.

Brief Summary:
This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose (SAD), multiple ascending dose (MAD), and 28-day safety study of orally administered DNL151 in healthy volunteers.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: DNL151 Drug: Placebo Phase 1

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.).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 186 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Of DNL151 in Healthy Volunteers
Actual Study Start Date : November 16, 2017
Actual Primary Completion Date : February 19, 2021
Actual Study Completion Date : February 19, 2021

Arm Intervention/treatment
Experimental: DNL151
Part A: Single-ascending dose cohorts; Part B: Multiple-ascending dose cohorts (10 days); Part C: Single-dose cohort; Part D: Additional multiple-dose cohort (28 days); Part E Multiple-ascending dose cohorts (14 days)
Drug: DNL151
oral dose(s)

Placebo Comparator: Placebo
Part A: Single-ascending dose cohorts; Part B: Multiple-ascending dose cohorts (10 days); Part C: Single-dose cohort; Part D: Additional multiple-dose cohort (28 days); Part E Multiple-ascending dose cohorts (14 days)
Drug: Placebo
oral dose(s)




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs [ Time Frame: Up to 42 days ]
  2. PK parameter: Maximum observed concentration (Cmax) of DNL151 in plasma [ Time Frame: Up to 42 days ]
  3. PK parameter: Time to maximum observed concentration (Tmax) of DNL151 in plasma [ Time Frame: Up to 42 days ]
  4. PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL151 in plasma (single dosing only) [ Time Frame: Up to 42 days ]
  5. PK parameter: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last]) of DNL151 in plasma [ Time Frame: Up to 42 days ]
  6. PK parameter: The area under the concentration-time curve over a dosing interval (AUC0-τ) of DNL151 in plasma (multiple dosing only) [ Time Frame: Up to 42 days ]
  7. PK parameter: Apparent terminal elimination half-life (t1/2) of DNL151 in plasma [ Time Frame: Up to 42 days ]

Secondary Outcome Measures :
  1. Concentration of DNL151 in cerebrospinal fluid (CSF) (following selected single and multiple doses) [ Time Frame: Up to 13 days ]
  2. The pharmacodynamics of DNL151 in whole blood as measured by the percent change from baseline in pS935 [ Time Frame: Up to 42 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Key Inclusion Criteria:

  • Body mass index 18.5 to 35.0 kg/m², inclusive, and body weight of at least 50.0 kg at screening
  • In good health, determined by no clinically significant findings from medical history, physical examination, and vital sign measurements
  • Women of non-childbearing potential and men using contraceptive measures

Key Exclusion Criteria:

  • History of clinically significant hematological, renal, pancreatic, gastrointestinal, hepatic, cardiovascular, metabolic, endocrine, immunological, allergic disease, or other major disorders
  • History of asthma, chronic obstructive pulmonary disease, or emphysema
  • Clinically significant neurologic disorder
  • History of stomach or intestinal surgery or resection
  • History of malignancy

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): NCT04557800


Locations
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Netherlands
Centre for Human Drug Research
Leiden, South Holland, Netherlands, 2333
PRA Health Sciences, Van Swietenlaan
Groningen, Netherlands, 9728
Sponsors and Collaborators
Denali Therapeutics Inc.
Investigators
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Study Director: Andres Cruz-Herranz Denali Therapeutics Inc.
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Responsible Party: Denali Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT04557800    
Other Study ID Numbers: DNLI-C-0001
2017-003730-82 ( EudraCT Number )
First Posted: September 22, 2020    Key Record Dates
Last Update Posted: March 7, 2022
Last Verified: February 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No