A Study to Evaluate the Bioavailability and Safety of DNL343 in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT04581772
• Recruitment Status: Completed
• First Posted: October 9, 2020
• Last Update Posted: June 11, 2021
• Sponsor: Denali Therapeutics Inc.
• Information provided by (Responsible Party): Denali Therapeutics Inc.

Tracking Information

• First Submitted Date: September 29, 2020
• First Posted Date: October 9, 2020
• Last Update Posted Date: June 11, 2021
• Actual Study Start Date: December 23, 2020
• Actual Primary Completion Date: June 4, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2020)

• PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma [ Time Frame: Up to 15 days ]
• PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma [ Time Frame: Up to 15 days ]
• PK Parameter: Area under the concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of DNL343 in plasma [ Time Frame: Up to 15 days ]
• PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma [ Time Frame: Up to 15 days ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 5, 2020)

• PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma in the fed versus fasted states [ Time Frame: Up to 15 days ]
• PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma in the fed versus fasted states [ Time Frame: Up to 15 days ]
• PK Parameter: Area under the concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of DNL343 in plasma in the fed versus fasted states [ Time Frame: Up to 15 days ]
• PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma in the fed versus fasted states [ Time Frame: Up to 15 days ]
• Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 15 days ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Bioavailability and Safety of DNL343 in Healthy Volunteers
• Official Title: A Phase 1 Open-Label, Randomized, Crossover Study to Evaluate the Bioavailability, Effect of Food, Palatability, and Safety of Various DNL343 Oral Formulations in Healthy Participants
• Brief Summary: This is a Phase 1 relative bioavailability study carried out in approximately 24 healthy male subjects and healthy female subjects of non childbearing potential to investigate the effects of formulation and food on the safety, tolerability, and pharmacokinetics (PK) of DNL343.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Healthy Volunteers

Intervention

• Drug: DNL343
  Multiple oral doses
• Drug: Placebo
  Single oral dose
• Drug: DNL343
  Single oral dose

Study Arms

• Experimental: Cohort A
  Interventions:

  • Drug: DNL343
  • Drug: Placebo
• Experimental: Cohort B
  Interventions:

  • Drug: DNL343
  • Drug: Placebo
• Experimental: Cohort C
  Intervention: Drug: DNL343

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 10, 2021): 31
• Original Estimated Enrollment (submitted: October 5, 2020): 24
• Actual Study Completion Date: June 4, 2021
• Actual Primary Completion Date: June 4, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Body mass index (BMI) ≥18.5 to < 30 kg/m2 and body weight of at least 50 kg
• For women: Must have been surgically sterilized or be postmenopausal.

Key Exclusion Criteria:

• History of clinically significant endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders
• History of malignancy, except fully resected basal cell carcinoma
• History of clinically significant neurologic or psychiatric diseases; head trauma with loss of consciousness; or clinically significant depression or suicidal ideation

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: New Zealand

Administrative Information

• NCT Number: NCT04581772
• Other Study ID Numbers: DNLI-F-0002
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Denali Therapeutics Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Denali Therapeutics Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Richard Tsai, MD; Denali Therapeutics Inc.

• PRS Account: Denali Therapeutics Inc.
• Verification Date: June 2021