A Bioavailability Study of MIV-711 Oral Formulations in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
This is a single-Center, Randomised, 4-Period, Phase 1 Study to Evaluate the Pharmacokinetics, Safety and Tolerability, and Effect of Food on Pharmacokinetics following Single Doses of MIV-711 Capsule and Tablet Formulations in Healthy Volunteers

Official Title
-----------------
A Single-Center, Randomised, 4-Period, Phase 1 Study to Evaluate the Pharmacokinetics, Safety and Tolerability, and Effect of Food on Pharmacokinetics Following Single Doses of MIV-711 Capsule and Tablet Formulations in Healthy Volunteers

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: MIV-711


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria (subset): Healthy, adult, male or female, 19-55 years of age, inclusive, at screening. Body mass index (BMI) ≥ 18.5 and ≤ 30.0 kg/m2 at screening. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee. If not a menopausal female or surgically sterile male or female, subjects must be willing to practice at least one of the in the CSP described highly effective methods of birth control for at least a (partner's) menstrual cycle before and for 3 months after study drug administration. For a female of non-childbearing potential: must have undergone one of the following sterilization procedures at least 6 months prior to the first dose: hysteroscopic sterilization; bilateral tubal ligation or bilateral salpingectomy; hysterectomy; bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 2 years prior to the first dose and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status as per PI or designee judgment. Exclusion Criteria (subset): History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee. History of any illness that, in the opinion of the PI or designee, that could affect the action, absorption, or disposition of MIV-711 or may confound the results of the study or poses an additional risk to the subject by their participation in the study. History or presence of known structural cardiac abnormalities, syncope, cardiac conduction problems (first, second, or third degree heart blocks, bundle branch block, or incomplete block, atrial fibrillation and/or paroxysmal atrial fibrillation, sick sinus syndrome or prolonged QTc interval), inappropriate sinus bradycardia, deviant ECG morphology or exercise related cardiac events. 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 dose and throughout the study. Medication listed as part of acceptable birth control methods will be allowed. Any drugs known to be inducers of CYP enzymes for 28 days prior to the first dose of study drug and throughout the study. Appropriate sources will be consulted by the PI or designee to confirm lack of PK/PD interaction with study drug. Acetaminophen (up to 2 g per 24 hour period) may be permitted during the study. Hormone replacement therapy will also be allowed. Subjects on a stable dose (at least 3 months) of thyroid medication will be allowed. An inability to follow a standardized diet and meal schedule or inability to fast, as required during the study.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MIV-711 ABCD<br>Subjects will first receive the tablet formulation under fasted conditions (A) followed by the tablet formulation administered under fed conditions (B). Thereafter they will receive the capsule formulation under fasted conditions (C) followed by the capsule formulation administered under fed conditions (D). | Drug: MIV-711<br>* MIV-711 administered as tablets and capsules at four occasions<br>|
| Experimental: MIV-711 CDAB<br>Subjects will first receive the capsule formulation under fasted conditions (C)followed by the capsule formulation administered under fed conditions (D). Thereafter they will receive the tablet formulation under fasted conditions (A) followed by the tablet formulation administered under fed conditions (B). | Drug: MIV-711<br>* MIV-711 administered as tablets and capsules at four occasions<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (t) (AUC0-t) | The PK of MIV-711 following administration of single oral doses of capsule and tablet formulations under fasting and fed conditions in healthy subjects. The evaluation will be made between the formulations. | 0 to 72 hours post dose | 
| Area under the concentration-time curve, from time 0 extrapolated to infinity (AUC0-inf) | The PK of MIV-711 following administration of single oral doses of capsule and tablet formulations under fasting and fed conditions in healthy subjects. The evaluation will be made between the formulations. | 0 to 72 hours post dose | 
| Maximum observed concentration (Cmax) | The PK of MIV-711 following administration of single oral doses of capsule and tablet formulations under fasting and fed conditions in healthy subjects. The evaluation will be made between the formulations. | 0 to 72 hours post dose | 
| Time to reach maximum observed concentration (Tmax) | The PK of MIV-711 following administration of single oral doses of capsule and tablet formulations under fasting and fed conditions in healthy subjects. The evaluation will be made between the formulations. | 0 to 72 hours post dose | 
| Apparent terminal elimination rate constant (Kel) | The PK of MIV-711 following administration of single oral doses of capsule and tablet formulations under fasting and fed conditions in healthy subjects. The evaluation will be made between the formulations. | 0 to 72 hours post dose | 
| Apparent terminal elimination half-life (T½) | The PK of MIV-711 following administration of single oral doses of capsule and tablet formulations under fasting and fed conditions in healthy subjects. The evaluation will be made between the formulations. | 0 to 72 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and severity of AEs/SAE | Safety and tolerability of MIV-711 measured by number and severity of AEs/SAEs | from study start until 7+/-2 days after the last study drug administration | 
| The number of clinically significant abnormal lab results | Safety and tolerability of MIV-711 measured by number of clinical significant abnormal lab results. | from study start until 7+/-2 days after the last study drug administration | 
| The number of clinically significant ECG abnormalities | Safety and tolerability of MIV-711 measured by number of clinical significant ECG abnormalities. | from study start until 7+/-2 days after the last study drug administration | 
| The number of clinically significant physical examination abnormalities | Safety and tolerability of MIV-711 measured by number of clinical significant physical examination abnormalities. | from study start until 7+/-2 days after the last study drug administration |