Drug-drug Interaction Study of TPOXX When Co-administered With Phosphate Binders

NCT04485039 | Completed Phase 4 Results FDA Drug

• 1 other identifier: SIGA-246-023
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

An open-label, drug-drug interaction study with TPOXX and phosphate binders.

Conditions

Smallpox

Outcome Measures

Primary Outcomes (2)

• AUC0-inf

  Area under the plasma concentration of vs. time curve (AUC) of TPOXX from 0 extrapolated to infinity

  Day 3

• Cmax

  Cmax - maximum observed plasma concentration of TPOXX

  Day 3

Secondary Outcomes (1)

• Adverse Events

  59 days

Study Arms (5)

TPOXX: oral antiviral

OTHER

Single oral dose of TPOXX 600 mg

Drug: Tecovirimat

TPOXX: oral antiviral and sevelamer carbonate

OTHER

Single oral dose of TPOXX 600 mg co-administered with single oral dose of 1600 mg sevelamer carbonate

Drug: Tecovirimat; Drug: sevelamer carbonate oral tablet

TPOXX: oral antiviral and sucroferric oxyhydroxide

OTHER

Single oral dose of TPOXX 600 mg co-administered with single oral dose of 500 mg sucroferric oxyhydroxide chewable tablet

Drug: Tecovirimat; Drug: sucroferric oxyhydroxide chewable tablet

TPOXX: oral antiviral and calcium acetate

OTHER

Single oral dose of TPOXX 600 mg co-administered with a single oral dose of 1334 mg calcium acetate

Drug: Tecovirimat; Drug: calcium acetate oral tablet

TPOXX: oral antiviral and lanthanum carbonate

OTHER

Single oral dose of TPOXX 600 mg co-administered with a single oral dose of 500 mg lanthanum carbonate chewable tablet

Drug: Tecovirimat; Drug: Lanthanum Carbonate Chewable Tablet

Interventions

Tecovirimat DRUG

oral antiviral

Also known as: TPOXX

TPOXX: oral antiviral; TPOXX: oral antiviral and calcium acetate; TPOXX: oral antiviral and lanthanum carbonate; TPOXX: oral antiviral and sevelamer carbonate; TPOXX: oral antiviral and sucroferric oxyhydroxide

sevelamer carbonate oral tablet DRUG

phosphate binder

Also known as: Renvela

TPOXX: oral antiviral and sevelamer carbonate

sucroferric oxyhydroxide chewable tablet DRUG

phosphate binder

Also known as: Velphoro

TPOXX: oral antiviral and sucroferric oxyhydroxide

calcium acetate oral tablet DRUG

phosphate binder

Also known as: PhosLo

TPOXX: oral antiviral and calcium acetate

Lanthanum Carbonate Chewable Tablet DRUG

phosphate binder

Also known as: Fosrenol

TPOXX: oral antiviral and lanthanum carbonate

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Each subject must meet all of the following criteria to be enrolled in this study:
• Subject is male or female 18 to 50 years of age, inclusive.
• Phosphorus levels within normal laboratory reference range.
• Women of childbearing potential have a negative human chorionic gonadotropin pregnancy test (serum) at the screening visit and a confirmatory negative serum pregnancy test on Day -1 of each period before receipt of study drug, and meet one of the following criteria:
• The subject or their partner has undergone surgical sterilization
• The subject is postmenopausal, defined as 12 consecutive months with no menses without an alternative medical cause and has a documented plasma follicle-stimulating hormone level \>40 IU/mL

You may not qualify if:

• Subjects meeting any of the following criteria will be excluded from the study:
• Subject is a female who is pregnant or breastfeeding or planning to become pregnant within 3 months after the last dose of study drug.
• Subject has a history of any clinically significant conditions including:
• Asthma treated with oral systemic steroids within the past 6 months
• Diabetes mellitus (type 1 or 2), with the exception of gestational diabetes
• Hypertension that is poorly controlled (repeat readings \>140 mm Hg systolic and/or \>90 mm Hg diastolic)
• Thyroidectomy or thyroid disease that required medication within the past 12 months
• Serious angioedema episodes within the previous 3 years or requiring medication in the previous 2 years
• Head trauma resulting in a diagnosis of traumatic brain injury other than concussion
• Frequent episodes of headache.
• Subject has received treatment in another clinical study of an investigational drug (or medical device) within 30 days or 5 half-lives (whichever is longer) before the first dose of study drug.
• Subject has a history of relevant drug and/or food allergies (ie, allergy to TPOXX or excipients, or any significant food allergy that could preclude a standard diet in the study site).
• Subject has any condition possibly affecting drug absorption (eg, previous surgery on the gastrointestinal tract, including removal of parts of the stomach, bowel, liver, gallbladder, or pancreas, with the exception of appendectomy).
• Subject has evidence or history of clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at time of the first dose of study drug), hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease. Exceptions to these criteria (eg, stable, mild joint disease unassociated with collagen vascular disease) may be made following discussions with the medical monitor.
• Subject has a history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or risk factors for torsades de pointes (eg, heart failure, hypokalemia).

Sponsors & Collaborators

• SIGA Technologies: lead
• Biomedical Advanced Research and Development Authority: collaborator
• PPD Development, LP: collaborator

Study Sites (1)

PPD Phase I Clinic

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

Smallpox

Interventions

tecovirimat; Sevelamer; sucroferric oxyhydroxide; calcium acetate; lanthanum carbonate

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Polyamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Emily Blum, Director of Clinical Development
• Organization: SIGA Technologies

eblum@siga.com

541-224-1305

Study Officials

• Dennis Hruby, PhD

  SIGA Technologies Chief Scientific Officer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 5 period crossover

Study Record Dates

• First Submitted: May 11, 2020
• First Posted: July 24, 2020
• Study Start: June 8, 2022
• Primary Completion: December 15, 2022
• Study Completion: April 23, 2023
• Last Updated: December 27, 2024
• Results First Posted: October 9, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)