Healthy Volunteer, Opioid-use Disorder
Conditions
Brief summary
The primary objectives for the study are: * Part I and Part II: Assess safety and tolerability of repeated doses of INDV-2000 in healthy volunteers. * Part III: Assess the safety and tolerability of repeated doses of INDV-2000 administered alone and with SUBOXONE sublingual (SL) film in an opioid use disorder (OUD) treatment seeking population.
Detailed description
The study will be conducted in 3 parts: Part I: Double-blind, placebo-controlled, randomized, multiple ascending dose study for 7 days of dosing with INDV-2000 in healthy volunteers. Part II: Double-blind, placebo-controlled, randomized, multiple ascending dose study for 28 days of dosing with INDV-2000 in healthy volunteers. Part III: This part is an open-label study in OUD treatment seeking individuals.
Interventions
DRUGINDV-2000
Capsule for oral administration
DRUGPlacebo
Capsule for oral administration
DRUGSUBOXONE® sublingual film
Administered either under the tongue (sublingual) or between the gum and cheek (buccal)
Sponsors
National Institute on Drug Abuse (NIDA)
Indivior Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Able to verbalize understanding of the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures, be able to comply with protocol requirements, rules and regulations of study site, and be likely to complete all the study interventions. 2. Female subjects of child-bearing potential who are sexually active with males must use, with their partner, a condom plus an approved method of effective contraception from the time of screening until 30 days after the last dose of Investigational Medicinal Product (IMP). The impact of IMP on the efficacy of hormonal contraceptives is unknown. Male subjects who are sexually active with female partners of child-bearing potential must use, with their partner, a condom plus an approved method of effective contraception from the time of screening until 90 days after the last dose of IMP and agree to not donate sperm over this time period. Effective methods of contraception are: 1. Combined (estrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal 2. Progestogen-only hormonal contraception: oral, injectable/implantable, or intrauterine hormone-releasing system (IUD) 3. Implantable intrauterine device (IUS) 4. Surgical sterilization (for example, vasectomy or bilateral tubal ligation) 5. Male condom with spermicidal gel/foam or with female cap or diaphragm (double barrier) 6. abstinence from heterosexual intercourse as a conscious choice and established pattern of lifestyle Part I and II only: 3. Healthy male or female. 4. Between 18 and 55 years of age inclusive. 5. Body mass index (BMI) within 18.0 to 32.0 kg/m\^2, inclusive (minimum weight of at least 50.0 kg at Screening). Part III only: 6. Male or female seeking treatment for OUD with a diagnosis of moderate or severe OUD by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria. 7. Between 18 and 65 years of age inclusive. 8. BMI within 18.0 to 35.0 kg/m\^2, inclusive (minimum weight of at least 50.0 kg at Screening).
Exclusion criteria
1. Have a medical history of clinically significant neurological, cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, or psychiatric disorder as judged by an Investigator. 2. Have clinically significant abnormal biochemistry, hematology or urinalysis results as judged by an Investigator or medically responsible physician. 3. Have a history of narcolepsy or other significant sleep disorders. 4. Have disorders that may interfere with drug absorption, distribution, metabolism and excretion (ADME) processes. 5. Positive test results for human immunodeficiency virus (HIV)-1/HIV-2 antibodies, hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCVAb). 6. Serious cardiac illness or other cardiac assessments including, but not limited to: 1. Uncontrolled arrhythmias. 2. History of congestive heart failure (CHF). 3. Myocardial infarction \<6 months from receipt of first dose of IMP 4. Uncontrolled symptomatic angina 5. QTcF \> 450 msec for males and \> 470 msec for females or history of prolonged QT syndrome. 7. Current active hepatic or biliary disease, including subjects with cholecystectomy \<90 days prior to Screening. 8. Concurrent treatment or treatment with an investigational drug within 30 days prior to the first dose of any study drug. 9. History of suicidal ideation within 30 days prior to providing written informed consent as evidenced by answering yes' to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) completed at the Screening Visit or history of a suicide attempt (per the C-SSRS) in the 6 months prior to informed consent. 10. Pregnant or lactating females. 11. Any consumption of food or drink containing poppy seeds, grapefruit or Seville oranges within 7 days prior to the IMP administration. 12. Treatment with any known drugs that are moderate or strong inhibitors/inducers of cytochrome P450 (CYP) 3A4 within 30 days prior to first dose of IMP. 13. Known allergy or hypersensitivity to IMP or its excipients. 14. Any condition that, in the opinion of an Investigator or medically responsible physician, would interfere with evaluation of the IMP or interpretation of subject safety or study results. 15. Affiliated with, or a family member of, site staff directly involved in the study, or anyone with a financial interest in the outcome of the study. 16. Subjects who are unable, in the opinion of an Investigator or medically responsible physician, to comply fully with the study requirements. 17. Participation in any other clinical study within 30 days prior to signing the informed consent form. 18. Current incarceration or pending incarceration/legal action that could prevent participation or compliance in the study. Part I and II only: 19. Regular alcohol consumption in males \> 21 units per week and females \> 14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine). 20. Positive test result for alcohol and/or any drugs of abuse at screening 21. Have a blood pressure reading outside of the following range: Systolic \< 86 or \> 149 mmHg; Diastolic \< 50 or \> 94 mmHg 22. Current smokers and those who have smoked within the last 90 days. Current users of e-cigarettes and nicotine replacement products, and those who have used these products within the last 90 days. 23. Blood donation of greater than 500 mL within 56 days or plasma donation within 7 days of screening; clinically significant anemia or low hemoglobin (\<11 g/dL for females, \<12 g/dL for males). 24. Healthy volunteers who are taking, or have taken, any prescribed or over-the-counter drugs (other than 2 g per day acetaminophen, hormone replacement therapy \[HRT\], hormonal contraception) or herbal remedies in the 14 days before IMP administration. Exceptions may apply on a case by case basis if considered not to interfere with the objectives of the study, as agreed by an Investigator and Sponsor's Medical Monitor. Part III only: 25. Regular alcohol consumption in males \> 27 units per week and females \> 20 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine). 26. Current substance use disorder, as defined by DSM-5 criteria, with any substances other than opioids, tobacco, cannabis, or alcohol, or dependence with any substance that would interfere with the completion of the study by judgment of the Investigator or medically responsible physician. 27. Current history of alcohol withdrawal within one year prior to screening. 28. Blood donation of greater than 500 mL within 56 days or plasma donation within 7 days of screening; clinically significant anemia or low hemoglobin (\< 10 g/dL for females, \< 12 g/dL for males). 29. Have a blood pressure reading outside of the following range: Systolic \< 86 or \> 159 mmHg; Diastolic \< 50 or \> 99 mmHg. Investigator should rule out acute changes resulting from opioid withdrawal. 30. Has total bilirubin ≥ 1.5 × upper limit of normal (ULN) (with direct bilirubin \> 1.3 mg/dL), alanine aminotransferase (ALT) ≥ 3 × ULN, aspartate aminotransferase (AST) ≥ 3 × ULN, serum creatinine \> 2 × ULN, or international normalized ratio (INR) \> 1.5 × ULN at Screening). 31. Received medication-assisted treatment for OUD (e.g., methadone, buprenorphine) in the 30 days prior to providing written informed consent. 32. Received any prior treatment with a buprenorphine implant or injection. 33. Treatment for OUD required by court order.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part I and Part II: Number of Participants With Adverse Events | From first dose of study drug up to 7 days after last dose (up to 14 days in Part I and 35 days in Part II). |
| Part III: Number of Participants With Adverse Events | From first dose of INDV-2000 up to 7 days after last dose (up to 18 days). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part I and Part II: Maximum Plasma Concentration (Cmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II, predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | Day 28 is only for Part II. |
| Part I and Part II: Time to Maximum Plasma Concentration (Tmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II, predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | Day 28 is only for Part II |
| Part I and Part II: Area Under the Plasma Concentration-time Curve (AUC0-τ) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II, predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | τ = 12 hours for BID dosing and 24 hours for QD dosing. Day 28 is only for Part II. |
Countries
United States
Participant flow
Pre-assignment details
The study was conducted in 3 parts: Part I and Part II in healthy volunteers, and Part III in treatment seeking individuals with opioid use disorder (OUD).
Participants by arm
| Arm | Count |
|---|---|
| Part I: INDV-2000 100 mg QD Healthy volunteers received INDV-2000 once daily for 7 days.
INDV-2000: 100 mg/capsule for oral administration | 9 |
| Part I: INDV-2000 100 mg BID Healthy volunteers received INDV-2000 twice daily for 7 days.
INDV-2000: 100 mg/capsule for oral administration | 9 |
| Part I: Placebo (Pooled) Healthy volunteers received placebo either once daily or twice daily for 7 days.
Placebo: Capsule for oral administration | 6 |
| Part II: INDV-2000 200 mg BID Healthy volunteers received INDV-2000 twice daily for 28 days.
INDV-2000: One 200 mg/capsule for oral administration | 9 |
| Part II: INDV-2000 400 mg BID Healthy volunteers received INDV-2000 twice daily for 28 days.
INDV-2000: Two 200 mg/capsule for oral administration | 9 |
| Part II: Placebo (Pooled) Healthy volunteers received placebo twice daily for 28 days.
Placebo: Either one or two capsules for oral administration | 6 |
| Part III: INDV-2000 400 mg BID + SUBOXONE SL A single cohort of treatment seeking participants with opioid use disorder (OUD) received SUBOXONE sublingual (SL) film for 6 days during the run-in period. Participants then received SUBOXONE SL film alone for 2 days, then SUBOXONE SL film and INDV-2000 for 7 days, followed by INDV-2000 dosing alone for 4 days.
INDV-2000: Two 200 mg/capsule for oral administration
SUBOXONE® sublingual film: Administered either under the tongue (sublingual) or between the gum and cheek (buccal) | 16 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Part I | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part II | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Part II | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part II | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part I: INDV-2000 100 mg QD | Part I: INDV-2000 100 mg BID | Part I: Placebo (Pooled) | Part II: INDV-2000 200 mg BID | Part II: INDV-2000 400 mg BID | Part II: Placebo (Pooled) | Part III: INDV-2000 400 mg BID + SUBOXONE SL | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 39.6 years STANDARD_DEVIATION 11.29 | 38.3 years STANDARD_DEVIATION 6.5 | 36.7 years STANDARD_DEVIATION 11.48 | 40.2 years STANDARD_DEVIATION 8.17 | 40.6 years STANDARD_DEVIATION 9 | 35.7 years STANDARD_DEVIATION 11.31 | 39.9 years STANDARD_DEVIATION 4.89 | 39.1 years STANDARD_DEVIATION 8.31 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 3 Participants | 7 Participants | 5 Participants | 2 Participants | 5 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | 2 Participants | 1 Participants | 4 Participants | 4 Participants | 11 Participants | 30 Participants |
| Region of Enrollment United States | 9 participants | 9 participants | 6 participants | 9 participants | 9 participants | 6 participants | 16 participants | 64 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Male | 7 Participants | 8 Participants | 5 Participants | 8 Participants | 6 Participants | 6 Participants | 12 Participants | 52 Participants |
| Weight | 78.18 kg STANDARD_DEVIATION 10.103 | 82.67 kg STANDARD_DEVIATION 11.63 | 86.20 kg STANDARD_DEVIATION 15.129 | 76.48 kg STANDARD_DEVIATION 5.833 | 82.00 kg STANDARD_DEVIATION 16.252 | 82.25 kg STANDARD_DEVIATION 13.536 | 86.24 kg STANDARD_DEVIATION 19.333 | 82.26 kg STANDARD_DEVIATION 14.226 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 | 0 / 6 | 0 / 9 | 0 / 9 | 0 / 6 | 0 / 16 |
| other Total, other adverse events | 5 / 9 | 2 / 9 | 3 / 6 | 8 / 9 | 8 / 9 | 2 / 6 | 5 / 16 |
| serious Total, serious adverse events | 1 / 9 | 0 / 9 | 0 / 6 | 0 / 9 | 0 / 9 | 0 / 6 | 0 / 16 |
Outcome results
Primary
Part I and Part II: Number of Participants With Adverse Events
Time frame: From first dose of study drug up to 7 days after last dose (up to 14 days in Part I and 35 days in Part II).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part I: INDV-2000 100 mg QD | Part I and Part II: Number of Participants With Adverse Events | Discontinuation | 0 Participants |
| Part I: INDV-2000 100 mg QD | Part I and Part II: Number of Participants With Adverse Events | Death | 0 Participants |
| Part I: INDV-2000 100 mg QD | Part I and Part II: Number of Participants With Adverse Events | Study drug-related | 5 Participants |
| Part I: INDV-2000 100 mg QD | Part I and Part II: Number of Participants With Adverse Events | Serious | 1 Participants |
| Part I: INDV-2000 100 mg QD | Part I and Part II: Number of Participants With Adverse Events | Severe | 1 Participants |
| Part I: INDV-2000 100 mg QD | Part I and Part II: Number of Participants With Adverse Events | Serious and Study drug-related | 0 Participants |
| Part I: INDV-2000 100 mg QD | Part I and Part II: Number of Participants With Adverse Events | Any TEAE | 5 Participants |
| Part I: INDV-2000 100 mg BID | Part I and Part II: Number of Participants With Adverse Events | Serious and Study drug-related | 0 Participants |
| Part I: INDV-2000 100 mg BID | Part I and Part II: Number of Participants With Adverse Events | Study drug-related | 0 Participants |
| Part I: INDV-2000 100 mg BID | Part I and Part II: Number of Participants With Adverse Events | Any TEAE | 2 Participants |
| Part I: INDV-2000 100 mg BID | Part I and Part II: Number of Participants With Adverse Events | Discontinuation | 0 Participants |
| Part I: INDV-2000 100 mg BID | Part I and Part II: Number of Participants With Adverse Events | Severe | 0 Participants |
| Part I: INDV-2000 100 mg BID | Part I and Part II: Number of Participants With Adverse Events | Serious | 0 Participants |
| Part I: INDV-2000 100 mg BID | Part I and Part II: Number of Participants With Adverse Events | Death | 0 Participants |
| Part I: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Serious | 0 Participants |
| Part I: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Death | 0 Participants |
| Part I: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Severe | 0 Participants |
| Part I: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Discontinuation | 0 Participants |
| Part I: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Study drug-related | 2 Participants |
| Part I: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Any TEAE | 3 Participants |
| Part I: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Serious and Study drug-related | 0 Participants |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Number of Participants With Adverse Events | Severe | 0 Participants |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Number of Participants With Adverse Events | Discontinuation | 1 Participants |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Number of Participants With Adverse Events | Death | 0 Participants |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Number of Participants With Adverse Events | Any TEAE | 8 Participants |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Number of Participants With Adverse Events | Serious | 0 Participants |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Number of Participants With Adverse Events | Study drug-related | 8 Participants |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Number of Participants With Adverse Events | Serious and Study drug-related | 0 Participants |
| Part II: INDV-2000 400 mg BID | Part I and Part II: Number of Participants With Adverse Events | Study drug-related | 6 Participants |
| Part II: INDV-2000 400 mg BID | Part I and Part II: Number of Participants With Adverse Events | Serious | 0 Participants |
| Part II: INDV-2000 400 mg BID | Part I and Part II: Number of Participants With Adverse Events | Discontinuation | 0 Participants |
| Part II: INDV-2000 400 mg BID | Part I and Part II: Number of Participants With Adverse Events | Any TEAE | 8 Participants |
| Part II: INDV-2000 400 mg BID | Part I and Part II: Number of Participants With Adverse Events | Serious and Study drug-related | 0 Participants |
| Part II: INDV-2000 400 mg BID | Part I and Part II: Number of Participants With Adverse Events | Severe | 0 Participants |
| Part II: INDV-2000 400 mg BID | Part I and Part II: Number of Participants With Adverse Events | Death | 0 Participants |
| Part II: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Study drug-related | 1 Participants |
| Part II: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Serious | 0 Participants |
| Part II: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Death | 0 Participants |
| Part II: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Discontinuation | 1 Participants |
| Part II: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Serious and Study drug-related | 0 Participants |
| Part II: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Any TEAE | 2 Participants |
| Part II: Placebo (Pooled) | Part I and Part II: Number of Participants With Adverse Events | Severe | 0 Participants |
Primary
Part III: Number of Participants With Adverse Events
Time frame: From first dose of INDV-2000 up to 7 days after last dose (up to 18 days).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part I: INDV-2000 100 mg QD | Part III: Number of Participants With Adverse Events | Any TEAE | 5 Participants |
| Part I: INDV-2000 100 mg QD | Part III: Number of Participants With Adverse Events | Serious | 0 Participants |
| Part I: INDV-2000 100 mg QD | Part III: Number of Participants With Adverse Events | Study-drug related | 2 Participants |
| Part I: INDV-2000 100 mg QD | Part III: Number of Participants With Adverse Events | Serious and Study-drug related | 0 Participants |
| Part I: INDV-2000 100 mg QD | Part III: Number of Participants With Adverse Events | Severe | 0 Participants |
| Part I: INDV-2000 100 mg QD | Part III: Number of Participants With Adverse Events | Discontinuation | 0 Participants |
| Part I: INDV-2000 100 mg QD | Part III: Number of Participants With Adverse Events | Death | 0 Participants |
Secondary
Part I and Part II: Area Under the Plasma Concentration-time Curve (AUC0-τ) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II
τ = 12 hours for BID dosing and 24 hours for QD dosing. Day 28 is only for Part II.
Time frame: Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II, predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: INDV-2000 100 mg QD | Part I and Part II: Area Under the Plasma Concentration-time Curve (AUC0-τ) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 1, AUC0-τ | 5800 hour*ng/mL | Geometric Coefficient of Variation 64.4 |
| Part I: INDV-2000 100 mg QD | Part I and Part II: Area Under the Plasma Concentration-time Curve (AUC0-τ) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 7, AUC0-τ | 5660 hour*ng/mL | Geometric Coefficient of Variation 56.8 |
| Part I: INDV-2000 100 mg BID | Part I and Part II: Area Under the Plasma Concentration-time Curve (AUC0-τ) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 1, AUC0-τ | 4760 hour*ng/mL | Geometric Coefficient of Variation 31.8 |
| Part I: INDV-2000 100 mg BID | Part I and Part II: Area Under the Plasma Concentration-time Curve (AUC0-τ) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 7, AUC0-τ | 5570 hour*ng/mL | Geometric Coefficient of Variation 26.7 |
| Part I: Placebo (Pooled) | Part I and Part II: Area Under the Plasma Concentration-time Curve (AUC0-τ) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 1, AUC0-τ | 9460 hour*ng/mL | Geometric Coefficient of Variation 34.7 |
| Part I: Placebo (Pooled) | Part I and Part II: Area Under the Plasma Concentration-time Curve (AUC0-τ) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 7, AUC0-τ | 8930 hour*ng/mL | Geometric Coefficient of Variation 43.2 |
| Part I: Placebo (Pooled) | Part I and Part II: Area Under the Plasma Concentration-time Curve (AUC0-τ) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 28, AUC0-τ | 11600 hour*ng/mL | Geometric Coefficient of Variation 42 |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Area Under the Plasma Concentration-time Curve (AUC0-τ) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 28, AUC0-τ | 12700 hour*ng/mL | Geometric Coefficient of Variation 31.4 |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Area Under the Plasma Concentration-time Curve (AUC0-τ) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 7, AUC0-τ | 12000 hour*ng/mL | Geometric Coefficient of Variation 43.2 |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Area Under the Plasma Concentration-time Curve (AUC0-τ) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 1, AUC0-τ | 11900 hour*ng/mL | Geometric Coefficient of Variation 44.9 |
Secondary
Part I and Part II: Maximum Plasma Concentration (Cmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II
Day 28 is only for Part II.
Time frame: Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II, predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: INDV-2000 100 mg QD | Part I and Part II: Maximum Plasma Concentration (Cmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 1 | 849 ng/mL | Geometric Coefficient of Variation 51.9 |
| Part I: INDV-2000 100 mg QD | Part I and Part II: Maximum Plasma Concentration (Cmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 7 | 967 ng/mL | Geometric Coefficient of Variation 34.3 |
| Part I: INDV-2000 100 mg BID | Part I and Part II: Maximum Plasma Concentration (Cmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 7 | 855 ng/mL | Geometric Coefficient of Variation 32.6 |
| Part I: INDV-2000 100 mg BID | Part I and Part II: Maximum Plasma Concentration (Cmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 1 | 759 ng/mL | Geometric Coefficient of Variation 36.3 |
| Part I: Placebo (Pooled) | Part I and Part II: Maximum Plasma Concentration (Cmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 1 | 1480 ng/mL | Geometric Coefficient of Variation 50.1 |
| Part I: Placebo (Pooled) | Part I and Part II: Maximum Plasma Concentration (Cmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 7 | 1570 ng/mL | Geometric Coefficient of Variation 49 |
| Part I: Placebo (Pooled) | Part I and Part II: Maximum Plasma Concentration (Cmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 28 | 1780 ng/mL | Geometric Coefficient of Variation 40 |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Maximum Plasma Concentration (Cmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 1 | 1830 ng/mL | Geometric Coefficient of Variation 43.8 |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Maximum Plasma Concentration (Cmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 7 | 1670 ng/mL | Geometric Coefficient of Variation 45.2 |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Maximum Plasma Concentration (Cmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 28 | 1920 ng/mL | Geometric Coefficient of Variation 36.2 |
Secondary
Part I and Part II: Time to Maximum Plasma Concentration (Tmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II
Day 28 is only for Part II
Time frame: Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II, predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part I: INDV-2000 100 mg QD | Part I and Part II: Time to Maximum Plasma Concentration (Tmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 1 | 4 hour |
| Part I: INDV-2000 100 mg QD | Part I and Part II: Time to Maximum Plasma Concentration (Tmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 7 | 3 hour |
| Part I: INDV-2000 100 mg BID | Part I and Part II: Time to Maximum Plasma Concentration (Tmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 7 | 1 hour |
| Part I: INDV-2000 100 mg BID | Part I and Part II: Time to Maximum Plasma Concentration (Tmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 1 | 2 hour |
| Part I: Placebo (Pooled) | Part I and Part II: Time to Maximum Plasma Concentration (Tmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 1 | 3 hour |
| Part I: Placebo (Pooled) | Part I and Part II: Time to Maximum Plasma Concentration (Tmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 7 | 4 hour |
| Part I: Placebo (Pooled) | Part I and Part II: Time to Maximum Plasma Concentration (Tmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 28 | 2 hour |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Time to Maximum Plasma Concentration (Tmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 7 | 2 hour |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Time to Maximum Plasma Concentration (Tmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 28 | 2 hour |
| Part II: INDV-2000 200 mg BID | Part I and Part II: Time to Maximum Plasma Concentration (Tmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II | Day 1 | 2 hour |