Coronary Heart Disease, Dyslipidemias
Conditions
Keywords
Atorvastatin, Cannabidiol, CBD, CHD, LDL-C
Brief summary
A Phase 1 study will assess the safety, tolerability, and pharmacokinetics of Atorvo+™ in healthy adult participants. .
Detailed description
This study will be testing an approved dose of atorvastatin (40 mg) and doses of CBD in the approved range (100 mg and 200 mg, approximately 1.7 mg/kg/day and 3.3 mg/kg/day for a 60 kg patient, respectively) in the study. A total of 24 participants are planned to be enrolled into 3 study arms. Eight (8) participants are planned to be randomized in each of Arms 1, 2, and 3. Each arm will consist of a 28-days Screening period, a 28-day treatment period, and a 14-day follow-up period. Investigational products (IPs) refer to all study treatments and will be administered at the following planned dose levels: * Arm 1: Atorvastatin (generic formulation) oral tablet 40 mg once daily for 28 days. * Arm 2: Atorvo+™ Low (40 mg Atorvastatin and 100 mg CBD) once daily for 28 days. * Arm 3: Atorvo+™ High (40 mg Atorvastatin and 200 mg CBD) once daily for 28 days.
Interventions
DRUGAtorvo+™ (Arm1)
Atorvo+™ is a combination product containing atorvastatin and cannabidiol (CBD).
DRUGAtorvo+™ +CBD (Arm 2)
Atorvo+™ is a combination product containing atorvastatin and cannabidiol (CBD).
DRUGAtorvo+™ +CBD (Arm 3)
Atorvo+™ is a combination product containing atorvastatin and cannabidiol (CBD).
Sponsors
Indication Bioscience LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Diagnosis and Main Criteria for Inclusion: Inclusion Criteria: To be eligible for this study, a participant must meet all of the following inclusion criteria: 1. Able to and willing to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures. 2. Male or female aged between 40 and 75 years (inclusive at the time of consent). 3. Nonsmoker (not used any tobacco products within 2 months prior to Screening). Participants who smoke ≤ 5 cigarettes or equivalent (eg, cigars, vaping, nicotine patches) per week can be included in the study at the discretion of the PI or designee if willing to abstain during inpatient stay. 4. Body mass index (BMI) \>18.0 and \<32.0 kg/m2 at Screening and body weight ≥50.0 kg and ≤ 120.0 kg. 5. Is judged by the Investigator to be in generally good health based on medical history, physical examination, vital sign parameters, ECG, laboratory parameters, and other relevant tests conducted at Screening. 6. Pulse between 50 and 100 beats per minute (bpm), inclusive at Screening. 7. Systolic blood pressure (BP) between 100 and 140 mmHg, diastolic BP between 50 and 90 mmHg inclusive, at Screening. For the purpose of qualifying any given participant for study participation, out-of-range vital signs may be repeated once. 8. No known allergic reaction to cannabis products (including tetrahydrocannabinol \[THC\], CBD, marijuana, and hashish) or EPIDIOLEX®. 9. Must have hepatic and renal clinical laboratory test results (total bilirubin and estimated glomerular filtrate rate \[eGFR\] by the CKD-EPI \[2021\] equation) within a laboratory defined normal range at Screening. Repeat testing at Screening is acceptable for out-of-range values following approval by the PI or designers. 10. Females must not be pregnant, lactating, or planning pregnancy, and if they are a woman of childbearing potential (WOCBP), must use acceptable, highly effective contraception from Screening until 93 days (90 days + approximately 5 half-lives) after the last IP administration. Effective forms of contraception are defined in Section 7.2.2. Females with same-sex partners (abstinence from penile-vaginal intercourse) are eligible when this is their preferred and usual lifestyle. Women of childbearing potential must have a negative serum hCG pregnancy test at Screening and negative urine test on Day -1. Women not of childbearing potential must be postmenopausal for ≥ 12 months (postmenopausal status is to be confirmed through testing of follicle-stimulating hormone \[FSH\] levels ≥ 40 IU/L at Screening for amenorrhoeic female participants), or otherwise permanently sterile (for which acceptable methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy). 11. Male participants who are sexually active with WOCBP must meet any of the following criteria: 1. Vasectomy for at least 6 months prior to enrolment and willing and able to use a condom. 2. Willing and able to use one of highly effective contraception methods. 3. Male participants with pregnant partners are not eligible. 12. Male participants must be willing not to donate sperm throughout the study and for 93 days (90 days + approximately 5 half-lives) after the last dose of IP. 13. Willing and able to adhere to all study requirements, including willingness to remain in the study unit for the entire duration of the confinement period. 14. Participant has a good venous access bilaterally.
Exclusion criteria
A participant who meets any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence, severity, and relationship of adverse events (AEs) | Baseline to End of study (Day 42) from first IP dose | — |
| Incidence of serious adverse events (SAEs) | Baseline to End of study (Day 42) from first IP dose | — |
| Incidence of adverse events of special interest (AESIs) | Baseline to End of study (Day 42) from first IP dose | This includes clinically significant abnormal values in liver function tests (LFTs) (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], total bilirubin), myopathy, myositis, myalgia, and type 2 diabetes |
| Number of participants with changes in laboratory parameters | Baseline to End of study (Day 42) from first IP dose | hematology, biochemistry, coagulation, and urinalysis), physical examination, vital signs (blood pressure \[BP\], heart rate \[HR\], respiratory rate \[RR\], and body temperature), electrocardiogram (ECG) parameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters-Elimination rate constant (Kel) | Baseline to End of study (Day 42) from first IP dose | — |
| Changes in Columbia-Suicide Severity Rating Scale (C-SSRS score) | Baseline to End of study (Day 42) from first IP dose | — |
| To evaluate mitochondrial oxidative stress in Atorvo+™ vs atorvastatin. | Baseline to End of study (Day 42) from first IP dose | This is measured by mean change in oxygen consumption rate (OCR) in Atorvo+ ™ vs atorvastatin (Baseline to EOS visit). Key parameters to be assessed- Basal respiration |
| PK parameters- Half-life (t½) | Baseline to End of study (Day 42) from first IP dose | — |
| PK Parameters- Maximum Plasma concentration (Cmax) | Baseline to End of study (Day 42) from first IP dose | — |
| PK Parameters- Time for maximum concentration (Tmax) | Baseline to End of study (Day 42) from first IP dose | — |
| PK Parameters- Area under Curve | Baseline to End of study (Day 42) from first IP dose | Area under curve to the last measurable concentration (AUC0-t), Area under the curve of concentration versus time from zero to infinity (AUC0-∞) and %AUC extra will be assessed. |
Countries
Australia
Outcome results
None listed