Clinical trial NCT04795037: First-In-Human Study of CU06-1004 Following Single and Multiple Ascending Doses in Healthy Volunteers
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, and Pharmacokinetic Study of Escalating Single and Multiple Doses of CU06-1004 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetic Macular Edema
Keywords: DME
Endothelial dysfunction blocker
Lead sponsor: Curacle Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: KCRN Research, LLC
First posted: 2021-03-12
Enrollment: 81
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: A Single Ascending Dose(SAD) study with 7 Cohorts including 1 Cohorts for Food effect (FE) assessment with 8 subjects each (6 active and 2 placebo) and A Multiple Ascending Dose(MAD) study with 3 Cohorts with 8 subjects each (6 active and 2 placebo).
Primary purpose: TREATMENT

Brief summary: This clinical trial is the first-in-human study of CU06-1004. The purpose of this phase 1 study is to assess the safety and tolerability of single and multiple ascending oral doses of CU06-1004 in healthy adult subjects.


Eligibility criteria: Inclusion Criteria:

1. Healthy, adult, male or female (of non-childbearing potential only), 19-55 years of age, inclusive, at screening.
2. Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at screening.
3. Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing and throughout the study, based on subject self-reporting.
4. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.
5. Female must be of non-childbearing potential and must have undergone one of the following sterilization procedures at least 6 months prior to the first dosing:

   * hysteroscopic sterilization;
   * bilateral tubal ligation or bilateral salpingectomy;
   * hysterectomy;
   * bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to the first dosing and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status.
6. A non-vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days after the last dosing.

   (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to the first dosing. A male who has been vasectomized less than 4 months prior to the first dosing must follow the same restrictions as a non-vasectomized male).
7. If male, must agree not to donate sperm from the first dosing until 90 days after the last dosing.
8. Able to swallow multiple capsules.
9. Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.

Exclusion Criteria:

1. Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
3. History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
4. History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing.
5. History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds.
6. Female subjects of childbearing potential.
7. Female subjects with a positive pregnancy test at screening or first check-in or who are lactating.
8. Positive urine drug or alcohol results at screening or first check-in.
9. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
10. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg, at screening.
11. Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.
12. QTcF interval is \>460 msec (males) or \>470 msec (females) or has ECG findings deemed abnormal with clinical significance by the PI or designee at screening.
13. Unable to refrain from or anticipates the use of:

    * Any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements (especially sulforaphane-containing supplement) beginning 14 days prior to the first dosing and throughout the study. After randomization, acetaminophen (up to 2 g per 24 hours) may be administered at the discretion of the PI or designee.
    * Food and beverages containing xanthines/caffeine for 24 hours prior to the first dosing (small amounts of caffeine derived from normal foodstuffs e.g.,250 mL/8 oz./1 cup decaffeinated coffee or other decaffeinated beverage, per day, with the exception of espresso; 45 g/1.5 oz. chocolate bar, per day, would not be considered a deviation to this restriction).
    * Food and beverages containing alcohol for 48 hours prior to the first dosing.
    * Food and beverages containing grapefruit/Seville orange for 14 days prior to the first dosing.
    * Food and beverages containing vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard) and charbroiled meats for 14 days prior to the first dosing.
14. Has received COVID-19 vaccine within 30 days of first dosing and until the end of the study.
15. Has been on a diet incompatible with the on-study diet, in the opinion of the PI or designee, within the 30 days prior to the first dosing and throughout the study.
16. Is lactose intolerant (FE cohort only).
17. Donation of blood or significant blood loss within 56 days prior to the first dosing.
18. Plasma donation within 7 days prior to the first dosing.
19. Participation in another clinical study within 30 days prior to the first dosing. The 30-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to the first dose of study drug in the current study.

Primary outcomes:
measure: The number and severity of treatment emergent adverse events (TEAEs)
timeFrame: From the date of first dose through 7 days after the last dose
Secondary outcomes:
measure: Maximum plasma concentration (Cmax)
timeFrame: Day 1 through Day 4 (SAD), Day 1 through Day 10 (MAD)
measure: Time to reach maximum plasma concentration (Tmax)
timeFrame: Day 1 through Day 4 (SAD), Day 1 through Day 10 (MAD)
measure: Area under the concentration-time curve (AUC)
timeFrame: Day 1 through Day 4 (SAD), Day 1 through Day 10 (MAD)
measure: Terminal elimination rate constant (Kel)
timeFrame: Day 1 through Day 4 (SAD), Day 1 through Day 10 (MAD)
measure: Terminal elimination half-life (t½)
timeFrame: Day 1 through Day 4 (SAD), Day 1 through Day 10 (MAD)
measure: Maximum plasma concentration (Cmax) under fed conditions
timeFrame: Day 1 through Day 4 (SAD)
measure: Area under the concentration-time curve (AUC) under fed conditions
timeFrame: Day 1 through Day 4 (SAD)
measure: Amount of unchanged drug excreted in the urine collection (Ae)
timeFrame: Day 1 through Day 4 (SAD), Day 1 through Day 10 (MAD)
measure: Renal Clearance (CLR)
timeFrame: Day 1 through Day 4 (SAD), Day 1 through Day 10 (MAD)
measure: Fraction of drug excreted unchanged in urine (Fe)
timeFrame: Day 1 through Day 4 (SAD), Day 1 through Day 10 (MAD)
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
affiliation: Curacle Co., Ltd.
name: Ji-Hye Kang, Ph.D
role: STUDY_DIRECTOR
References:
citation: Maganti L, Panebianco DL, Maes AL. Evaluation of methods for estimating time to steady state with examples from phase 1 studies. AAPS J. 2008;10(1):141-7. doi: 10.1208/s12248-008-9014-y. Epub 2008 Feb 28.
citation: Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm. 1987 Dec;15(6):657-80. doi: 10.1007/BF01068419.