Safety, Tolerability and PK of TPOXX in Adults Weighing More Than 120 KG

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Brief Title

Safety, Tolerability and PK of TPOXX in Adults Weighing More Than 120 KG

Official Title

A Post Marketing Study of the Safety, Tolerability, and Pharmacokinetics of TPOXX In Adult Subjects Weighing More Than 120 KG

Brief Summary

      Safety and PK study in adults weighing more than 120 kg
    

Detailed Description

      The primary objective of this study is to determine the pharmacokinetic (PK) profile of 600
      mg oral TPOXX (3 × 200-mg capsules) administered twice daily (BID) for 7 days in adult
      subjects weighing more than 120 kg to determine if a change in dosing regimen would be needed
      in these patients.

      Secondary:

      The secondary objective of this study is to evaluate the safety and tolerability of 600 mg
      oral TPOXX administered BID for 7 days in healthy adult subjects weighing more than 120 kg.
    

Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

Area under the plasma concentration vs. time curve (AUC) from time 0 to the last quantifiable measurement (AUC0-t)

Secondary Outcome

 Number of subjects with AEs as assessed by CTCAE

Condition

Smallpox

Intervention

Tpoxx

Study Arms / Comparison Groups

 TPOXX
Description:  TPOXX 600 mg BID x 7 days

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

34

Start Date

July 19, 2019

Completion Date

December 5, 2019

Primary Completion Date

December 5, 2019

Eligibility Criteria

        Inclusion Criteria:

          1. Subject is male or female between 18 and 50 years of age, inclusive.

          2. Subject has a body weight >120 kg at screening, at check-in on Day -1, and prior to
             dosing on Day 1.

          3. Women of childbearing potential, have a negative β human chorionic gonadotropin
             pregnancy test (serum) at the screening visit and a confirmatory negative serum
             pregnancy test on Day -1 before receipt of study drug, and meet 1 of the following
             criteria:

               1. The subject or their partner has undergone surgical sterilization

               2. 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

               3. The subject agrees to be abstinent (ie, heterosexually inactive or women in a
                  religious order)

               4. The subject agrees to consistently use 1 of the following methods of
                  contraception from the beginning of screening (which they had been consistently
                  using for at least 30 days before the first dose of study drug) through 30 days
                  after the last dose of study drug:

             i. Condoms, male or female, with a spermicide NOTE: For male subjects, condoms must be
             used for 90 days after the last dose of study drug.

             ii. Diaphragm or cervical cap with spermicide

             iii. Intrauterine device with spermicide

             iv. Oral contraceptives or other hormonal methods NOTE: Subject must agree to use an
             additional nonhormonal method of contraception in conjunction with oral
             contraceptives.

             v. Male sexual partner who had undergone a vasectomy at least 3 months before
             screening

          4. Male subjects must agree to not donate sperm from the first dose of study drug through
             90 days after the last dose of study drug.

          5. Subject is considered by the investigator to be in good general health as determined
             by medical history (no hospitalizations for chronic medical conditions in the previous
             2 years), clinical laboratory results, vital sign measurements, 12-lead
             electrocardiogram (ECG) results, and physical examination findings at screening.

          6. Subject agrees to comply with all protocol requirements.

          7. Subject is able to provide written informed consent.

          8. Subject agrees to comply with the dietary requirements.

          9. Subject does not intend to lose

        Exclusion Criteria:

        Subjects meeting any of the following criteria will be excluded from the study:

          1. Subject is a female who is pregnant or breastfeeding or planning to become pregnant
             within 3 months after the last dose of study drug.

          2. 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

               -  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.

          3. 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.

          4. Subject has been previously enrolled in any clinical study involving TPOXX
             (tecovirimat).

          5. Subject has a history of relevant drug and/or food allergies (ie, allergy to
             tecovirimat or excipients, or any significant food allergy that could preclude a
             standard diet in the study site).

          6. 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).

          7. 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.

             Page 10

          8. Subject has a history of cardiac disease, symptomatic or asymptomatic arrhythmias,
             syncopal episodes, or risk factors for torsades de pointes (eg, heart failure,
             hypokalemia).

          9. Subject has a family history of sudden cardiac death, not clearly due to acute
             myocardial infarction.

         10. Subject has a seizure disorder or history of seizures (does not include childhood
             febrile seizures) or a past history that increases seizure risks such as significant
             head injury that caused loss of consciousness or other changes in the subject's daily
             function, concussion, stroke, central nervous system infection or disease, or alcohol
             or drug abuse or family history of idiopathic seizures.

         11. Subject has a history of a peptic ulcer or significant gastrointestinal bleed.

         12. Subject has a bleeding disorder diagnosed by a doctor (eg, factor deficiency,
             coagulopathy, or platelet disorder requiring special precautions) or significant
             bruising or bleeding difficulties with blood draws.

         13. Subject has a malignancy that is active, or treated malignancy for which there is not
             reasonable assurance of sustained cure, or malignancy that is likely to recur during
             the period of the study (subject should be in complete remission for at least 5
             years).

         14. Subject has neutropenia or other blood dyscrasia determined to be clinically
             significant by the investigator.

         15. Subject has used any of the following prohibited medications from within 7 days (or 5
             half-lives, whichever is longer) before the first dose of study drug: antidiabetic
             medication; anticoagulants; anticonvulsants; substrates of the breast cancer
             resistance protein transporter including methotrexate, mitoxantrone, imatinib,
             irinotecan, lapatinib, rosuvastatin, sulfasalazine, and topotecan; substrates of
             CYP2C8 including repaglinide, paclitaxel, Montelukast, pioglitazone, rosiglitazone;
             and substrates of CYP2C19 including S-mephenytoin, clobazam, diazepam, rabeprazole,
             voriconazole, lansoprazole, and omeprazole. Medications not listed here that are known
             (or thought) to be CYP3A4 substrates may be allowed at the investigator's discretion,
             after consultation with the medical monitor, if administration poses little to no risk
             to the subject.

         16. Subject has a history of drug or alcohol abuse or dependency within the last year
             before screening.

         17. Subject has a history of an eating disorder.

         18. Subject has a current or recent (<30 days before screening) history of clinically
             significant bacterial, fungal, or mycobacterial infection.

         19. Subject has a current clinically significant viral infection.

         20. Subject has a known clinically significant chronic viral infection (eg, human T cell
             lymphotropic virus I or II).

         21. Subject has consumed grapefruit or grapefruit juice, Seville orange or Seville
             orange-containing products (eg, marmalade), or caffeine- or xanthine-containing
             products within 48 hours before the first dose of study drug or throughout the study.

         22. Subject has used any prescription (excluding hormonal birth control) or
             over-the-counter medication (including herbal or nutritional supplements) within 14
             days before the first dose of study drug.

         23. Subject demonstrates long-term use (≥14 consecutive days) of glucocorticoids including
             oral or parenteral prednisone or equivalent (>20 mg total dose per day) or high-dose
             inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within
             the preceding 1 month (low-dose [≤800 mcg/day of beclomethasone dipropionate or
             equivalent] inhaled and topical steroids are allowed).

         24. Subject has donated >450 mL blood or blood components within 30 days before the first
             dose of study drug. The investigator should instruct subjects who participate in this
             study to not donate blood or blood components for 4 weeks after the completion of the
             study.

         25. Subject is a smoker or has used nicotine or nicotine-containing products (eg,
             cigarettes, electronic vapor cigarettes, cigars, chewing tobacco, snuff, nicotine
             patches, or nicotine gum) within 6 months before the first dose of study drug.

         26. Subject has consumed pomegranate or pomegranate juice, pomelo fruits or pomelo juice,
             or alcohol within 72 hours before the first dose of study drug.

         27. Subject reports participation in strenuous activity or contact sports within 24 hours
             before the first dose of study drug.

         28. Subject has known hepatitis B or C infection or positive test for hepatitis B surface
             antigen, hepatitis C virus antibody, or human immunodeficiency virus type 1 or 2
             antibodies at screening.

         29. Subject has a positive test result for amphetamines (including methamphetamines and
             ecstasy/methylenedioxymethamphetamine), barbiturates, benzodiazepines, cannabinoids
             (including tetrahydrocannabinol), cocaine metabolites, opiates (including heroin,
             codeine, and oxycodone), or alcohol at screening or check-in.

         30. Subject has any of the following laboratory test results within 28 days before the
             first dose of study drug:

               -  Estimated serum creatinine clearance (Cockcroft-Gault) <90 mL/min

               -  Creatinine in males >1.7 mg/dL and in females >1.4 mg/dL (1.3 times the upper
                  central laboratory reference range)

               -  Hemoglobin ≤10% of the lower central laboratory reference range

               -  White blood cell count not within the central laboratory reference range

               -  Absolute neutrophil count <1000 cells/mm3

               -  Platelets not within ±10% of central laboratory reference range

               -  Alanine aminotransferase >1.5 times above the upper central laboratory reference
                  range

               -  Aspartate aminotransferase >1.5 times above the upper central laboratory
                  reference range

               -  Alkaline phosphatase >20% above the upper central laboratory reference range

               -  Hemoglobin A1c ≥7.0%

               -  Cholesterol ≥300 mg/dL and low-density lipoprotein ≥190 mg/dL.

         31. Subject has a blood pressure considered to be clinically significant by the
             investigator. Blood pressure may be retested twice in the sitting position at 5-minute
             intervals.

         32. Subject has a resting heart rate of <40 beats per minute or >100 beats per minute at
             screening.

         33. Subject has an abnormal ECG at screening that is determined by the investigator to be
             clinically significant.

         34. Male subject has a QTcF >450 ms or female subject has a QTcF >470 ms at screening or
             Day -1.

         35. In the opinion of the investigator, the subject is not suitable for entry into the
             study.
      

Gender

All

Ages

20 Years - 50 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Dennis Hruby, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04392739

Organization ID

SIGA-246-022


Responsible Party

Sponsor

Study Sponsor

SIGA Technologies

Collaborators

 Biomedical Advanced Research and Development Authority

Study Sponsor

Dennis Hruby, PhD, Study Director, SIGA Chief Scientific Officer


Verification Date

May 2020