Healthy Volunteers
Conditions
Brief summary
The main purpose of the study is to characterize the interaction between RO7049389 and the cholesterol-lowering drug, pitavastatin, in healthy volunteers. There is no intended clinical benefit to this study. The total duration of the study for each participant is approximately 12 weeks.
Interventions
DRUGRO7049389
RO7049389 will be taken orally, in tablet form, BID on Days 1-6 of Period 2.
DRUGPitavastatin
Pitavastatin will be taken orally, in tablet form, once on Day 1 of Period 1, and once on Day 4 of Period 2.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy, as judged by the Investigator. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, and based on the laboratory safety test results at screening and Day -1 * Body mass index (BMI) between 18 to 30 kg/m2 (inclusive) at screening * Female participants: 1) Must be either surgically sterile (by means of hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy) or post-menopausal for at least one year (defined as amenorrhea \>/=12 consecutive months without another cause, and confirmed by follicle-stimulating hormone (FSH) level. 2) Participants must not be pregnant or lactating. * Male participants: 1) Female partners must not be pregnant or lactating. 2) Must agree to remain abstinent (refrain from heterosexual intercourse) or must agree to use a condom with spermicide during the treatment period and for at least 28 days after the last dose of study drug with female partners of childbearing potential. 3) Must agree to refrain from donating sperm during the treatment period and for at least 28 days after the last dose of study drug
Exclusion criteria
* Have a history or symptoms of any clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, oncologic or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study treatment; or of interfering with the interpretation of data * Confirmed (based on the average of 3 separate resting BP measurements in a supine position, after at least 5 minutes rest) systolic BP greater than 140 or less than 90 mmHg, and diastolic BP greater than 90 or less than 50 mmHg at screening and Day -1 * Personal history or family history of congenital long QT syndrome and/or cardiac sudden death * History of Gilbert's syndrome * Participants who have had significant acute infection, e.g., influenza, local infection, acute gastrointestinal symptoms or any other clinically significant illness within two weeks of dose administration * Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies (non-active hay fever is acceptable) * Taking any herbal medications or substances (e.g., tea) or supplements (including vitamins), or traditional Chinese medicines (TCM) or over-the-counter (OTC) medications within 14 days of first dosing or within 5 times the elimination half-life of the medication prior to first dosing, whichever is longer * History of having received any systemic anti-neoplastic (including radiation) or immunemodulatory treatment (including systemic oral or inhaled corticosteroids) \</=6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study * Are currently enrolled in or have participated in any other clinical study involving an investigational product or in any other type of medical research within the last 30 days or 5 half lives (whichever is longer) * Donation or loss of blood or blood products in excess of 500 mL within 3 months of screening and for the duration of the study * Positive test for drugs of abuse (including recreational drugs) and/or positive alcohol test and/or positive cotinine test at screening and on Day -1 * Positive test at screening of any of the following: Hepatitis A virus (HAV IgM Ab), hepatitis B virus (HBsAg or HBcAb), hepatitis C virus (HCV RNA or HCV Ab) or human immunodeficiency virus (HIV-1 and HIV-2 Ab) * History of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol) and/or drug abuse within 12 months of screening * Use of \>5 cigarettes or equivalent nicotine-containing product per day prior to screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Period 2: Elimination Half-Life (T1/2) of Pitavastatin | Period 2 Day 4 |
| Period 1: Time to Maximum Concentration (Tmax) of Pitavastatin | Period 1 Day 1 |
| Period 1: Apparent Total Clearance (CL/F) of Pitavastatin | Period 1 |
| Period 1: Volume of Distribution (V/F) of Pitavastatin | Period 1 Day 1 |
| Period 1: Elimination Half-Life (T1/2) of Pitavastatin | Period 1 Day 1 |
| Period 2: Maximum Plasma Concentration (Cmax) of Pitavastatin | Period 2 Day 4 |
| Period 2: Plasma Concentration Versus Time (Area Under the Curve, AUC0-inf) of Pitavastatin | Period 2 Day 4 |
| Period 2: Time to Maximum Concentration (Tmax) of Pitavastatin | Period 2 Day 4 |
| Period 2: Apparent Total Clearance (CL/F) of Pitavastatin | Period 2 Day 4 |
| Period 2: Volume of Distribution (V/F) of Pitavastatin | Period 2 Day 4 |
| Period 1: Maximum Plasma Concentration (Cmax) of Pitavastatin | Period 1 Day 1 |
| Period 1: Plasma Concentration Versus Time (Area Under the Curve, AUC0-inf) of Pitavastatin | Period 1 Day 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Period 2: Cmax of RO7049389 | Period 2 Days 3-4 | — |
| Period 2: AUC-tau of RO7049389 | Period 2 Days 3-4 | — |
| Period 1: Cmax of Pitavastatin Lactone | Period 1 Day 1 | — |
| Period 1: AUC0-inf of Pitavastatin Lactone | Period 1 Day 1 | — |
| Period 1: AUC Ratio of Pitavastatin Lactone to Pitavastatin | Period 1 Day 1 | — |
| Period 2: Cmax of Pitavastatin Lactone | Period 2 Day 4 | — |
| Period 2: AUC0-inf of Pitavastatin Lactone | Period 2 Day 4 | — |
| Period 2: AUC Ratio of Pitavastatin Lactone to Pitavastatin | Period 2 Day 4 | — |
| Percentage of Participants With Adverse Events (AEs) | From the start of Period 1 through safety follow-up (Period 2, Day 34) | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. |
Countries
United States
Participant flow
Recruitment details
This study recruited healthy adult participants at one site in the United States.
Pre-assignment details
This study had two periods. Period 1: Participants received a single dose of pitavastatin, followed by a washout period of 7-21 days. Period 2: Participants received a single dose of pitavastatin along with a twice-daily dose of RO7049389.
Participants by arm
| Arm | Count |
|---|---|
| Pitavastatin/RO7049389 Period 1: Participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 days and up to 21 days.
Period 2: Participants received RO7049389 on Days 1-6. Participants also received a single dose of pitavastatin on Day 4. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 2 | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Pitavastatin/RO7049389 |
|---|---|
| Age, Continuous | 39.2 Years STANDARD_DEVIATION 14.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 7 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
Period 1: Apparent Total Clearance (CL/F) of Pitavastatin
Time frame: Period 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 1: Apparent Total Clearance (CL/F) of Pitavastatin | 25.4 L/h | Geometric Coefficient of Variation 39.9 |
Primary
Period 1: Elimination Half-Life (T1/2) of Pitavastatin
Time frame: Period 1 Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 1: Elimination Half-Life (T1/2) of Pitavastatin | 14.3 h | Geometric Coefficient of Variation 32.4 |
Primary
Period 1: Maximum Plasma Concentration (Cmax) of Pitavastatin
Time frame: Period 1 Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 1: Maximum Plasma Concentration (Cmax) of Pitavastatin | 23.8 ng/mL | Geometric Coefficient of Variation 42.7 |
Primary
Period 1: Plasma Concentration Versus Time (Area Under the Curve, AUC0-inf) of Pitavastatin
Time frame: Period 1 Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 1: Plasma Concentration Versus Time (Area Under the Curve, AUC0-inf) of Pitavastatin | 78.6 h*ng/mL | Geometric Coefficient of Variation 41 |
Primary
Period 1: Time to Maximum Concentration (Tmax) of Pitavastatin
Time frame: Period 1 Day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pitavastatin/RO7049389 | Period 1: Time to Maximum Concentration (Tmax) of Pitavastatin | 1.5 hours (h) |
Primary
Period 1: Volume of Distribution (V/F) of Pitavastatin
Time frame: Period 1 Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 1: Volume of Distribution (V/F) of Pitavastatin | 525 Liters (L) | Geometric Coefficient of Variation 41.3 |
Primary
Period 2: Apparent Total Clearance (CL/F) of Pitavastatin
Time frame: Period 2 Day 4
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 2: Apparent Total Clearance (CL/F) of Pitavastatin | 15.6 L/h | Geometric Coefficient of Variation 45 |
Primary
Period 2: Elimination Half-Life (T1/2) of Pitavastatin
Time frame: Period 2 Day 4
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 2: Elimination Half-Life (T1/2) of Pitavastatin | 9.78 h | Geometric Coefficient of Variation 49 |
Primary
Period 2: Maximum Plasma Concentration (Cmax) of Pitavastatin
Time frame: Period 2 Day 4
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 2: Maximum Plasma Concentration (Cmax) of Pitavastatin | 33.5 ng/mL | Geometric Coefficient of Variation 52.7 |
Primary
Period 2: Plasma Concentration Versus Time (Area Under the Curve, AUC0-inf) of Pitavastatin
Time frame: Period 2 Day 4
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 2: Plasma Concentration Versus Time (Area Under the Curve, AUC0-inf) of Pitavastatin | 129 h*ng/mL | Geometric Coefficient of Variation 50.7 |
Primary
Period 2: Time to Maximum Concentration (Tmax) of Pitavastatin
Time frame: Period 2 Day 4
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pitavastatin/RO7049389 | Period 2: Time to Maximum Concentration (Tmax) of Pitavastatin | 2 h |
Primary
Period 2: Volume of Distribution (V/F) of Pitavastatin
Time frame: Period 2 Day 4
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 2: Volume of Distribution (V/F) of Pitavastatin | 220 L | Geometric Coefficient of Variation 59.3 |
Secondary
Percentage of Participants With Adverse Events (AEs)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: From the start of Period 1 through safety follow-up (Period 2, Day 34)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pitavastatin/RO7049389 | Percentage of Participants With Adverse Events (AEs) | 39 Percentage of Participants |
Secondary
Period 1: AUC0-inf of Pitavastatin Lactone
Time frame: Period 1 Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 1: AUC0-inf of Pitavastatin Lactone | 193 h*ng/mL | Geometric Coefficient of Variation 27.4 |
Secondary
Period 1: AUC Ratio of Pitavastatin Lactone to Pitavastatin
Time frame: Period 1 Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Pitavastatin/RO7049389 | Period 1: AUC Ratio of Pitavastatin Lactone to Pitavastatin | 2.45 Ratio |
Secondary
Period 1: Cmax of Pitavastatin Lactone
Time frame: Period 1 Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 1: Cmax of Pitavastatin Lactone | 14.4 ng/mL | Geometric Coefficient of Variation 23.5 |
Secondary
Period 2: AUC0-inf of Pitavastatin Lactone
Time frame: Period 2 Day 4
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 2: AUC0-inf of Pitavastatin Lactone | 81.7 h*ng/mL | Geometric Coefficient of Variation 19.9 |
Secondary
Period 2: AUC Ratio of Pitavastatin Lactone to Pitavastatin
Time frame: Period 2 Day 4
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Pitavastatin/RO7049389 | Period 2: AUC Ratio of Pitavastatin Lactone to Pitavastatin | 0.636 Ratio |
Secondary
Period 2: AUC-tau of RO7049389
Time frame: Period 2 Days 3-4
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pitavastatin/RO7049389 | Period 2: AUC-tau of RO7049389 | RO7049389 | 62700 h*ng/mL | Geometric Coefficient of Variation 92.8 |
| Pitavastatin/RO7049389 | Period 2: AUC-tau of RO7049389 | RO7049389 + Pitavastatin | 68500 h*ng/mL | Geometric Coefficient of Variation 81.8 |
Secondary
Period 2: Cmax of Pitavastatin Lactone
Time frame: Period 2 Day 4
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin/RO7049389 | Period 2: Cmax of Pitavastatin Lactone | 6.39 ng/mL | Geometric Coefficient of Variation 24.4 |
Secondary
Period 2: Cmax of RO7049389
Time frame: Period 2 Days 3-4
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pitavastatin/RO7049389 | Period 2: Cmax of RO7049389 | RO7049389 | 15400 ng/mL | Geometric Coefficient of Variation 58.1 |
| Pitavastatin/RO7049389 | Period 2: Cmax of RO7049389 | RO7049389 + Pitavastatin | 17600 ng/mL | Geometric Coefficient of Variation 48.4 |