A Study Evaluating the Relative Bioavailability of Lofexidine Granules for Reconstitution Compared to LUCEMYRA (Lofexidine) Tablets and the Effect of Food on the Bioavailability of the Lofexidine Granules for Reconstitution

A Study to Evaluate the Relative Bioavailability of a Test Formulation of Lofexidine Granules for Reconstitution and the Effect of Food on the Bioavailability of the Test Formulation in Healthy Adult Subjects

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04188730

Enrollment

Registered

2019-12-06

Start date

2021-02-16

Completion date

2021-03-26

Last updated

2022-06-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Normal Healthy Volunteers

Brief summary

The purpose of this open-label, single-dose, randomized, three-treatment, three-period, four-sequence, crossover study is to evaluate the relative bioavailability of a test formulation of lofexidine granules for reconstitution (oral) and LUCEMYRA tablets under fasted conditions and to evaluate the effect of food on the relative bioavailability of lofexidine granules for reconstitution (oral) when administered under fed compared to fasted conditions.

Interventions

DRUGLofexidine (granules for reconstitution)

All subjects will be administered one 0.36 mg dose of lofexidine granules for reconstitution.

DRUGLUCEMYRA (lofexidine) tablets

All subjects will be administered one 0.36 mg dose of LUCEMYRA (lofexidine) tablets.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 50 Years

Healthy volunteers

Yes

Inclusion criteria

1. Males and females, 18-50 years of age, inclusive, with a Body Mass Index (BMI) of 20.0-35.0 kg/m², inclusive. 2. Female subjects must meet at least one of the following criterion: * Agree to abstain from sexual intercourse from screening and throughout the duration of the study. * Have used and agree to continue to use a reliable method of contraception (e.g., condom with spermicide, IUD, hormonal contraceptives) for at least 30 days before initial dosing and throughout the duration of the study. * Surgically sterile (bilateral oophorectomy or hysterectomy, bilateral tubal ligation or Essure® device placement at least 3 months prior to initial dosing). * At least 1 year postmenopausal and have a documented FSH level ≥ 40 mIU/mL at screening. 3. Good health as determined by lack of clinically significant abnormalities in health assessments performed at screening. 4. Signed and dated informed consent form, which meets all criteria of current FDA regulations.

Exclusion criteria

1. Females who are pregnant, lactating, or likely to become pregnant during the study. 2. History of allergy or sensitivity to lofexidine or any component of the study drug or history of any drug hypersensitivity or intolerance which, in the opinion of the Investigator, would compromise the safety of the subject or the study. 3. Significant history or current evidence of chronic infectious disease, system disorders, or organ dysfunction, especially cardiovascular disorders (e.g., severe coronary insufficiency, recent myocardial infarction \[within 1 year before initial dosing\], cerebrovascular disease), respiratory disorders, congenital long QT syndrome, diabetes, hepatic or renal disorders (e.g., chronic renal failure). 4. Pulse \< 50 bpm or symptomatic bradycardia, as determined by the Investigator. 5. Clinically significant history of hypotension, as determined by the Investigator, or has a sitting/supine systolic blood pressure \< 90 mmHg and/or diastolic blood pressure \< 60 mmHg, or hypertension, as determined by the Investigator, or has sitting/supine systolic blood pressure \> 190 mmHg and/or diastolic \> 95 mmHg; determined at screening. 6. Experiences reduction of systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg within 3 minutes of standing from a resting (sitting or supine) position; determined at screening. 7. 12-lead ECG, conducted in triplicate, considered by the Investigator to be clinically significant (e.g., second or third degree heart block, uncontrolled arrhythmia) or has a QTcF (Fridericia's correction) interval \> 440 msec in 2 of the 3 ECGs performed; determined at screening. 8. Clinically significant history or presence of any gastrointestinal disease or history of malabsorption within the last year, as determined by the Investigator. 9. History of any psychiatric disorders occurring within the last two years that required the subject to be hospitalized or treated with medication. 10. Subject has history of suicidality based on responses provided on the Columbia-Suicide Severity Rating Scale (C-SSRS), or is at risk for self-harm or harm to others based on clinical interview, at the discretion of the Investigator. 11. Ingestion of grapefruit-containing food or beverages (e.g., Fresca®) within 7 days before dosing. 12. Drug or alcohol addiction requiring treatment in the 12 months before initial dosing. 13. History of excessive alcohol consumption (on average more than 14 units of alcohol/week) during the past 12 months. 14. Positive test results for HIV, Hepatitis B surface antigen, or Hepatitis C antibody. 15. Positive test results for drugs of abuse (benzodiazepines, cocaine, cannabinoids/THC, opiates and at screening only: amphetamines, barbiturates, methadone and phencyclidine).

Design outcomes

Primary

Measure	Time frame	Description
Time to Maximum Plasma Concentration (Tmax)	Day 1 through Day 3 for Periods I, II, III.	Time to peak plasma concentration (h) collection time at which Cmax is first observed.
First-order Terminal Half-life (T½)	Mean from Day 1 through Day 3 for Periods I, II, III.	—
Mean Maximum Plasma Concentration (Cmax)	Mean from Day 1 through Day 3 for Periods I, II, III.	The peak exposure plasma concentrations (Cmax) of lofexidine were observed and measured.
First-order Terminal Rate Constant (λz)	Mean from Day 1 through Day 3 for Periods I, II, III.	—
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-t)	Day 1 through Day 3 for Periods I, II, III.	Areas under the plasma concentration-time curve from time zero to the time of last measurable concentration (AUC0-t)
Area Under the Plasma Concentration-time Curve From Time Zero to Time Infinity (AUC0-∞)	Mean from Day 1 through Day 3 for Periods I, II, III.	—

Secondary

Measure	Time frame	Description
Occurrence of Adverse Events (AEs)	Total from occurrences assessed daily after each dosing for Periods 1-3, as well as end of study (22 days)	Number of Subjects dosed for each Treatment groups: Treatment A = 15 subjects dosed; Treatment B = 16 subjects dosed; Treatment C = 15 subjects dosed

Countries

United States

Participant flow

Participants by arm

Arm	Count
All Study Participants 16 individuals were enrolled in this crossover study. Each subject was eligible to participate in all 3 Treatment Groups (Treatment A, Treatment B, Treatment C).	16
Total	16

Baseline characteristics

Characteristic	All Study Participants
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	16 Participants
Age, Continuous	35.1 years STANDARD_DEVIATION 7.9
Body Mass Index (BMI)	28.5 kg/m^2 STANDARD_DEVIATION 3.2
Height	175.1 cm STANDARD_DEVIATION 8.4
Race (NIH/OMB) American Indian or Alaska Native	3 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	9 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	4 Participants
Sex: Female, Male Female	3 Participants
Sex: Female, Male Male	13 Participants
Tobacco Users No	16 Count of participants
Tobacco Users Yes	0 Count of participants
Weight	88.0 kg STANDARD_DEVIATION 14.6

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 15	0 / 16	0 / 15
other Total, other adverse events	3 / 15	8 / 16	7 / 15
serious Total, serious adverse events	0 / 15	0 / 16	0 / 15

Outcome results

Primary

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-t)

Areas under the plasma concentration-time curve from time zero to the time of last measurable concentration (AUC0-t)

Time frame: Day 1 through Day 3 for Periods I, II, III.