Single Ascending Dose and Multiple Ascending Dose Study of Niclosamide Inhalation Powder in Healthy Adult Subjects

NCT05168644 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: TFF-N1-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 (healthy adult volunteers), 2-part, double-blind, randomized, placebo controlled trial to evaluate the safety and pharmacokinetic (PK) profiles of escalating single doses of Niclosamide Inhalation Powder versus placebo (SAD part) and escalating multiple doses of Niclosamide Inhalation Powder versus placebo (MAD part). SAD part will be initiated first and includes a sentinel design. MAD part will not utilize a sentinel design unless the data monitoring committee requests the addition of sentinels. The MAD part will be initiated once the lowest doses from SAD part are deemed safe.

Conditions

Healthy

Outcome Measures

Primary Outcomes (9)

• Number of participants who experience Adverse Events (AEs), Serious Adverse Events (SAEs) and withdrawals due to AEs

  Number of AEs, SAEs, and discontinuation due to AEs

  Baseline through study completion, up to 43 days

• Number of participants who experience vital sign abnormalities

  Number of participants with potentially clinically significant vital sign values

  Baseline through study completion, up to 43 days

• Number of participants who experience pulse oximetry abnormalities

  Number of participants with potentially clinically significant pulse oximetry values

  Baseline through study completion, up to 43 days

• Mean change from baseline in forced expiratory volume (FEV1)

  Spirometry used to measure FEV1 lung function

  Baseline through study completion, up to 43 days

• Mean change from baseline in forced vital capacity (FVC)

  Spirometry used to measure FVC lung function

  Baseline through study completion, up to 43 days

• Mean change from baseline in FEV1/FVC ratio

  Spirometry used to measure FEV1 and FVC lung function

  Baseline through study completion, up to 43 days

• Mean change from baseline in QTcF changes via ECG

  Number of participants with potentially clinically significant ECG values

  Baseline through study completion, up to 43 days

• Number of participants who experience physical examination abnormalities

  Number of participants with potentially clinically significant physical examination findings

  Baseline through study completion, up to 43 days

• Number of participants who experience laboratory test abnormalities

  Number of participants with potentially clinically significant laboratory test results

  Baseline through study completion, up to 43 days

Secondary Outcomes (13)

• PK of Niclosamide in plasma: Area under the plasma-concentration time curve (AUC)

  Baseline through study completion, up to 43 days

• PK of Niclosamide in plasma: Area under the concentration time curve, from time 0 to the last observed non-zero concentration (AUC0-tlast)

  Baseline through study completion, up to 43 days

• PK of Niclosamide in plasma: Maximum observed concentration (Cmax)

  Baseline through study completion, up to 43 days

• PK of Niclosamide in plasma: Trough or minimum concentration (Ctrough)

  Baseline through study completion, up to 43 days

• PK of Niclosamide in plasma: Concentration at the end of the dosing interval (Ct)

  Baseline through study completion, up to 43 days

Study Arms (2)

Drug: Niclosamide Inhalation Powder

EXPERIMENTAL

PART A (SAD): Niclosamide Inhalation Powder will be supplied as one to six capsules. Each capsule contains either 0.25 mg or 1 mg of Niclosamide Inhalation Powder and will be administered with a Plastiape RS00 Dry Powder inhaler. Doses may require multiple inhalations. All inhalations must be conducted within a 20-minute period. SAD subjects will receive a single dose of study medication. Subjects in Cohort 1 will receive 0.5 mg, Cohort 2: 2 mg, Cohort 3: 6 mg. PART B (MAD): Niclosamide Inhalation Powder will be supplied as one to six capsules. Each capsule contains either 0.25 mg or 1 mg of Niclosamide Inhalation Powder and will be administered with a Plastiape RS00 Dry Powder inhaler. Doses may require multiple inhalations. All inhalations must be conducted within a 20-minute period. MAD subjects will receive Niclosamide Inhalation Powder BID for a total of 9 doses. Subjects in Cohort 4 will receive 3 mg BID, Cohort 5: 6 mg BID.

Drug: Niclosamide Inhalation Powder

Drug: Placebo

PLACEBO COMPARATOR

PART A (SAD): Placebo will be supplied as one to six capsules. Each capsule contains Placebo inhalation powder and will be administered with a Plastiape RS00 Dry Powder inhaler. Doses may require multiple inhalations. All inhalations must be conducted within a 20-minute period. SAD subjects (Part A) will receive a single dose of Placebo. PART B (MAD): Placebo inhalation powder will be supplied as one to six capsules. Each capsule contains Placebo inhalation powder and will be administered with a Plastiape RS00 Dry Powder inhaler. Doses may require multiple inhalations. All inhalations must be conducted within a 20-minute period. MAD subjects (Part B) will receive Placebo inhalation powder BID for a total of 9 doses.

Drug: Placebo

Interventions

Niclosamide Inhalation Powder DRUG

Investigational drug will be supplied as capsules, each capsule contains 0.25 mg or 1 mg of Niclosamide Inhalation Powder. The capsules will be administered with the provided breath actuated Plastiape RS00 Model 8 Dry Powder Inhaler device.

Drug: Niclosamide Inhalation Powder

Placebo DRUG

Placebo will be supplied as capsules, each capsule will contain no active ingredient. The capsules will be administered with the provided breath actuated Plastiape RS00 Model 8 Dry Powder Inhaler device.

Drug: Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Agree to use acceptable contraception or is not able to bear children.
• Body mass index (BMI) within ≥ 18.0 kg/m2 and ≤ 30.0 kg/m2 at Screening (body weight of at least 50.0 kg and no more than120 kg at Screening).
• Non-smoker or ex-smoker (stopped using nicotine products for at least 12 months prior to the first study drug administration and throughout the study).
• Have no clinically significant diseases, including asthma, captured in the medical history or on the physical examination, visual examination, clinical laboratory assessments, and/or ECG.
• A forced expiratory volume during the first second (FEV1) ≥ 80% at Screening and Check-in.

You may not qualify if:

• Female who is lactating, is pregnant or planning to become pregnant according to the pregnancy test at Screening or prior to the first study drug administration.
• Is mentally or legally incapacitated or unable to provide informed consent.
• History or presence of alcoholism or drug abuse within the past 2 years prior to the first study drug administration.
• History or presence of hypersensitivity or idiosyncratic reaction to niclosamide or any portion of the placebo.
• Has had surgery or any medical condition within 6 months prior to first study drug administration which may affect the absorption, distribution, metabolism, or elimination of the study drug, in the opinion of the PI or designee.
• Use of albuterol or a similar bronchodilator.
• Immunization with a COVID-19 vaccine in the 14 days prior to the first study drug administration.
• Scheduled immunization with a COVID-19 vaccine (first or second dose) during the study that, in the opinion of an investigator, could potentially interfere with subject participation, subject safety, study results, or any other reason.
• History or allergy of rare hereditary problems of galactose and/or lactose intolerance, lactase deficiency or glucose-galactose malabsorption.
• Unable to refrain from or anticipates the use of:
• Any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dosing and throughout the study.
• Seasonal use of albuterol or other similar inhalers throughout study participation, beginning 14 days prior to the first dosing or 5 half-lives, whichever is longer.
• Use of St. John's wort in the 28 days prior to the first study drug administration.
• Positive Screening results for tuberculosis, HIV Ag/Ab combo, hepatitis B surface antigen or hepatitis C virus tests, or a positive test for alcohol, cotinine, and/or drugs of abuse.
• Participation in another clinical study within 30 days prior to the first study drug administration. The 30-day window will be derived from the date of the last study drug administration.

Sponsors & Collaborators

• TFF Pharmaceuticals, Inc.: lead

Study Sites (1)

Altasciences

Mount Royal, Quebec, Canada

Location

Study Officials

• Dale Christensen, PhD

  TFF Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The investigators, study coordinators, study subjects and the Sponsor will be blinded to treatment assignment.
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: Eight (8) subjects will participate in each of the 3 dose escalations. Subjects will be randomized to receive either Niclosamide Inhalation Powder or placebo by inhalation (6 active, 2 placebo per group of 8). Part B: Eight (8) subjects will participate in each of the 2 dose escalations. Subjects will be randomized to receive either Niclosamide Inhalation Powder or placebo by inhalation (6 active, 2 placebo per group of 8).

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: December 23, 2021
• Study Start: November 14, 2021
• Primary Completion: January 26, 2022
• Study Completion: January 26, 2022
• Last Updated: February 2, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)