Clinical trial NCT05077865: Single Ascending and Multiple Dose Study to Evaluate Safety, Tolerability, and PK of MYMD1 in Healthy Male and Female Adult Subjects
Official title: A Double-blind, Placebo-controlled, Randomized, Single Ascending and Multiple Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Oral Dose of MYMD1 Capsules in Healthy Male and Female Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hashimoto Disease
Lead sponsor: TNF Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-10-14
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized, placebo-controlled study
Primary purpose: TREATMENT

Brief summary: Double-blind, placebo-controlled, single ascending and multiple dose study. Approximately 32 healthy adult male and female subjects will be given a single capsule of MYMD1 to determine its safety, tolerability, and pharmacokinetic properties. The study data will guide the establishment of an optimum therapeutic dose.

Detailed description: A single-center, double-blind, placebo-controlled, single ascending and multiple-dose study to evaluate the safety, tolerability, and pharmacokinetics of a single oral dose of MYMD1 capsule in healthy male and female adult subjects. Each subject will participate in the study for approximately 7-8 weeks, including a Screening period of up to 30 days, a confinement period of 2 or 5 days, and a follow-up period of approximately 5 days. In each of Cohorts 1-3, 8 subjects will be administered a single dose of either MYMD1 (N=6 in each cohort) or Placebo (N=2 in each cohort), under fasted conditions. Subjects in Cohort 4 will be administered either MYMD1 (N=6) or Placebo (N=2) on Days 1, 2, 3, 4, and 5. Each subject will participate in only 1 of the 4 cohorts during the study. Anticipated dosing levels will be 150mg (Cohort 1); 300mg (Cohort 2); 250mg (Cohort 3); and 600mg (Cohort 4).

Eligibility criteria: Inclusion Criteria:

1. Provide written ICF.
2. Is a male or female aged 18 to 65 years.
3. Have a stable medical history and general health as judged by the Investigator on the basis of physical examination, medical history, ECG, and the results of clinical laboratory (chemistry,hematology, coagulation, and urinalysis) testing performed at Screening.
4. Body mass index of 18 to 31 kg/m2, inclusive.
5. Have estimated glomerular filtration rate (mL/min/1.73m2) or estimated creatinine clearance ≥90 mL.
6. Have normal hepatic function (alanine aminotransferase: 10 to 35 U/L, aspartate aminotransferase: 9 to 46 U/L, total protein: 6.1 to 8.1 g/dL, alkaline phosphatase: 40 to 115 U/L, direct bilirubin: \<0.2 mg/dL, and total bilirubin: 0.2 to 1.2 mg/dL).
7. Have adequate peripheral venous access.
8. Test negative for human immunodeficiency virus, hepatitis C virus antibodies, and hepatitis B surface antigen.
9. Test negative for drugs of abuse, including oxycodone, tricyclic anti-depressants, methadone, opiates, marijuana, phencyclidines, barbiturates, methamphetamine, ecstasy, amphetamine, cocaine, and benzodiazepine.
10. Be willing and able to complete all study assessments and procedures and to communicate effectively with the Investigator and study center staff.
11. Male participants and female participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception -

Exclusion Criteria:

1. Have an allergy to any of the study treatment ingredients.
2. Are unable to swallow capsules.
3. Have an elective medical procedure scheduled during the study. Bariatric surgery is also excluded.
4. Currently abusing drugs or alcohol, and/or have a history of drug or alcohol dependence within 6 months of entering this study.
5. Have any history of seizure disorder that has required medical treatment after 18 years of age.
6. Current smoker or smokeless tobacco user, ie, no use of tobacco within 30 days of study entry.
7. Have participated in any drug or medical device-related clinical study within 30 days of study entry.
8. Have values on standard clinical laboratory assessments that are deemed medically significant (show evidence of untreated significant medical illness or pose a risk of significant intercurrent illness during the study in the opinion of the Investigator).
9. Have any significant medical condition that could in the Investigator's opinion interfere with the study or put the subject at a significant risk. These may include, but not limited to the following: active malignant disease, current use of immune-suppressing drugs, currently taking opioid pain medication, and active seizure disorder.
10. On ECG, QTcF \>450 ms or the presence of clinically significant abnormalities as determined by the Investigator (Screening or Day -1).
11. Elevation of BP, ie, supine systolic BP \>145 mmHg and/or diastolic BP \>92 mmHg, or heart rate \>100 beats per minute at rest (Screening or Day -1). Readings that fall outside these ranges will be allowed to enter the study if they are health candidates at the Investigator's discretion.
12. Have gastrointestinal malabsorption.
13. Have abnormal renal function (defined as estimated glomerular filtration rate \<90 mL/min/1.73m2 or estimated creatinine clearance \<90 mL) and/or abnormal hepatic function at baseline.
14. Treatment with any prescription or nonprescription drugs, including vitamins, minerals, or herbal and dietary supplements, within 14 days or 5 half-lives of Day 1, whichever is longer, except Tylenol.
15. Use within 30 days prior to Day 1 of any drugs or substances, including grapefruit juice, that are known to strongly inhibit or induce cytochrome P450 (CYP) enzymes. If there is any question as to whether or a not a substance is permitted, please review the product labeling (if applicable) and consult the Sponsor.
16. Donation of blood or any blood product within 56 days of Day 1.
17. Willing to use effective contraception as in from Day -1 until 90 days after receiving study treatment.
18. Once it is confirmed that the subject meets eligibility for check-in, the subject will return approximately 5 to 7 days prior to their scheduled Day -1 to complete a COVID-19 test. All subjects will be required to have a negative test prior to check-in. A positive test will result in exclusion from the study.

Primary outcomes:
measure: Adverse Events
timeFrame: Cohorts 1,2,3: Continuous through 13 days (includes 10 days post-discharge); Cohort 4: Continuous through 16 days (includes 10 days post-discharge)
measure: Number of subjects with changes in clinical laboratory values - Serum Chemistry: BUN, Creatinine, Glucose, Magnesium, Cholesterol, Calcium, Uric Acid, C-Reactive Protein, T Bili, D Bili, Phosphate, and Triglycerides.
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Number of subjects with changes in clinical laboratory values - Serum Chemistry: albumin, globulin, Total protein.
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Number of subjects with changes in clinical laboratory values - Serum Chemistry: Electrolytes
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Number of subjects with changes in clinical laboratory values - Serum Chemistry: Creatine Kinase muscle/brain (MB) fraction
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Number of subjects with changes in clinical laboratory values - Serum Chemistry: Gamma Glutamyl Transferase (GTT), Lactate dehydrogenase, Aspartate Aminotransferase, Alanine aminotransferase, Alkaline phosphatase, Creatine kinase, and Amylase
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Number of Subjects with changes in clinical laboratory values - Hematology: Red Blood Cell (RBC) count
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Number of subjects with changes in clinical laboratory values - Hematology: Platelet count, White Blood Cell count
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Number of subjects with changes in clinical laboratory values - Hematology: Hematocrit, Reticulocytes
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Number of subjects with changes in clinical laboratory values - Hematology: Mean corpuscular volume, Absolute Neutrophils, Absolute Lymphocytes, Absolute Monocytes, Absolute Eosinophils, and Absolute Basophils
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Number of subjects with changes in clinical laboratory values - Hematology: Mean corpuscular hemoglobin
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Number of subjects with changes in clinical laboratory values - coagulation: Fibrinogen
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Number of subjects with changes in clinical laboratory values - coagulation: Prothrombin time, Activated partial thromboplastin time, Thrombin time
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Urinalysis: Microscopic
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Urinalysis: Urobilinogen
timeFrame: Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
measure: Changes in Electrocardiogram (ECG): Heart Rate
timeFrame: Cohorts 1, 2, 3: 0.5, 1, 4, 24, 48, 168 hrs; Cohort 4: 0.5, 1, 4, 24, 48, 72, 96, 240 hrs.
measure: Changes in Electrocardiogram (ECG): PR, RR, QRS, QT, QTcF, and QTcB
timeFrame: Cohorts 1, 2, 3: 0.5, 1, 4, 24, 48, 168 hrs; Cohort 4: 0.5, 1, 4, 24, 48, 72, 96, 240 hrs.
measure: Change from Baseline QTcF and QTcB
timeFrame: Cohorts 1, 2, 3: 0.5, 1, 4, 24, 48, 168 hrs; Cohort 4: 0.5, 1, 4, 24, 48, 72, 96, 240 hrs.
measure: Changes in Physical examination: Head, eye, ear, nose, and throat
timeFrame: Cohorts 1, 2, 3: Days -1, 2, 3, 8; Cohort 4: Days -1, 3, 5, 6, 11
measure: Changes in Physical examination: Cardiovascular
timeFrame: Cohorts 1, 2, 3: Days -1, 2, 3, 8; Cohort 4: Days -1, 3, 5, 6, 11
measure: Changes in Physical examination: General Appearance
timeFrame: Cohorts 1, 2, 3: Days -1, 2, 3, 8; Cohort 4: Days -1, 3, 5, 6, 11
measure: Changes in Physical examination: Respiratory
timeFrame: Cohorts 1, 2, 3: Days -1, 2, 3, 8; Cohort 4: Days -1, 3, 5, 6, 11
measure: Changes in Physical examination: Gastrointestinal
timeFrame: Cohorts 1, 2, 3: Days -1, 2, 3, 8; Cohort 4: Days -1, 3, 5, 6, 11
measure: Changes in Physical examination: Body Weight
timeFrame: Cohorts 1, 2, 3: Days -1, 8; Cohort 4: Days -1, 5, 6
measure: Pharmacokinetics: AUC
timeFrame: Cohorts 1, 2, 3: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48 hrs; Cohort 4: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hrs.
measure: Pharmacokinetics: Cmax
timeFrame: Cohorts 1, 2, 3: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48 hrs; Cohort 4: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hrs.
measure: Pharmacokinetics: tmax
timeFrame: Cohorts 1, 2, 3: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48 hrs; Cohort 4: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hrs.
measure: Pharmacokinetics: t1/2
timeFrame: Cohorts 1, 2, 3: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48 hrs; Cohort 4: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hrs.
measure: Pharmacokinetics: CL/F
timeFrame: Cohorts 1, 2, 3: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48 hrs; Cohort 4: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hrs.
measure: Pharmacokinetics: Volume of Distribution (V2/F )
timeFrame: Cohorts 1, 2, 3: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48 hrs; Cohort 4: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hrs.
measure: Pharmacokinetics: Urine presence of MYMD1
timeFrame: Cohorts 1, 2, 3, 4: Hours 0-4, 4-8, 8-12, 12-16, 16-24, 24-32, 32-40, 40-48; Additional timepoints for Cohort 4 only: Day 3 - Hours 0-8, 8-16, 16-24, Day 4 - Hours 0-8, 8-16, 16-24, Day 5 - Hours 0-8, 8-16, 16-24.
measure: Vital signs: Oral Temperature (degrees Centigrade)
timeFrame: Cohorts 1, 2, 3: Hours 0.25, 0.5, 1, 2, 4, 6, 12, 24, 48, 168; Cohort 4: Hours 0.5, 1, 2, 4, 6, 12, 24, 48, 72, 120, 240.
measure: Vital Signs: Pulse Rate
timeFrame: Cohorts 1, 2, 3: Hours 0.25, 0.5, 1, 2, 4, 6, 12, 24, 48, 168; Cohort 4: Hours 0.5, 1, 2, 4, 6, 12, 24, 48, 72, 120, 240.
measure: Vital signs: Blood Pressure
timeFrame: Cohorts 1, 2, 3: Hours 0.25, 0.5, 1, 2, 4, 6, 12, 24, 48, 168; Cohort 4: Hours 0.5, 1, 2, 4, 6, 12, 24, 48, 72, 120, 240.
measure: Vital signs: Respiratory Rate
timeFrame: Cohorts 1, 2, 3: Hours 0.25, 0.5, 1, 2, 4, 6, 12, 24, 48, 168; Cohort 4: Hours 0.5, 1, 2, 4, 6, 12, 24, 48, 72, 120, 240.
Secondary outcomes:
measure: Pharmacokinetics: AUC
timeFrame: Cohorts 1, 2, 3: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48; Cohort 4: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96
measure: Pharmacokinetics: Cmax
timeFrame: Cohorts 1, 2, 3: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48; Cohort 4: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96
measure: Pharmacokinetics: Tmax
timeFrame: Cohorts 1, 2, 3: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48; Cohort 4: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96
measure: Pharmacokinetics: T1/2
timeFrame: Cohorts 1, 2, 3: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48; Cohort 4: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96
measure: Pharmacokinetics: CL/F
timeFrame: Cohorts 1, 2, 3: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48; Cohort 4: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96
measure: Pharmacokinetics: Vz/F
timeFrame: Cohorts 1, 2, 3: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48; Cohort 4: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96
measure: Biomarker Assessment: Tissue Necrosis Factor (TNF) alpha (TNF-α)
timeFrame: Cohorts 1, 2, 3: Hours 2 and 48; Cohort 4: Hours 2, 48, 96, and 120.
measure: Biomarker Assessment: Pyridyloxobutyl (POB) adducts in hemophilia
timeFrame: Cohorts 1, 2, 3: Hours 2 and 48; Cohort 4: Hours 2, 48, 96, and 120.
measure: Cardiovascular: QTcF
timeFrame: Cohorts 1, 2, 3: 0.5, 1, 4, 24, 48, 168 hrs; Cohort 4: 0.5, 1, 4, 24, 48, 72, 96, 240 hrs.
Other outcomes:
Locations:
city: Clearwater
country: United States
facility: Clinical Research of West Florida, Inc
state: Florida
Study officials:
affiliation: Clinical Research of West Florida, Inc
name: Leonard Dunn, MD
role: PRINCIPAL_INVESTIGATOR
References: