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

• Sponsor: Denali Therapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04581772
• Collaborator: (none)
• Enrollment: 31
• Location: 1
• Arms: 3
• Actual Duration (Months): 5.4
• Patients Per Site Per Month: 5.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: DNL343; Drug: Placebo; Drug: DNL343	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 23, 2020
• Actual Primary Completion Date: Jun 4, 2021
• Actual Study Completion Date: Jun 4, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A	Drug: DNL343; Multiple oral doses; Drug: Placebo; Single oral dose
Experimental: Cohort B	Drug: DNL343; Multiple oral doses; Drug: Placebo; Single oral dose
Experimental: Cohort C	Drug: DNL343; Single oral dose

Outcome Measures

Primary Outcome Measures

1. PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma [Up to 15 days]

2. PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma [Up to 15 days]

3. PK Parameter: Area under the concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of DNL343 in plasma [Up to 15 days]

4. PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma [Up to 15 days]

Secondary Outcome Measures

1. PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma in the fed versus fasted states [Up to 15 days]

2. PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma in the fed versus fasted states [Up to 15 days]

3. 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 [Up to 15 days]

4. 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 [Up to 15 days]

5. Incidence of treatment-emergent adverse events (TEAEs) [Up to 15 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Auckland Clinical Studies Ltd.	Grafton	Auckland	New Zealand

Sponsors and Collaborators

• Denali Therapeutics Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Denali Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT04581772
• Other Study ID Numbers: DNLI-F-0002
• First Posted: Oct 9, 2020
• Last Update Posted: Jun 11, 2021
• Last Verified: Jun 1, 2021

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

Study Results

No Results Posted as of Jun 11, 2021