Pharmacokinetics and Bioequivalence of Molnupiravir, 200 mg Capsules and Lagevrio, 200 mg Capsules in Healthy Volunteers

NCT05412173 | Completed

• 1 other identifier: MOL-05-02-2021
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The study aimed for:

1. 1.Comparative evaluation of the safety of the drug Molnupiravir, capsules, 200 mg (JSC "Valenta Pharm", Russia), and Lagevrio, capsules, 200 mg (Merck Sharp \& Dohme (UK) Limited, UK), based on the analysis of adverse events (AEs);
2. 2.Comparative assessment of pharmacokinetic parameters and bioequivalence of the drug Molnupiravir, capsules, 200 mg (Valenta Pharm JSC, Russia), and Lagevrio, capsules, 200 mg (Merck Sharp \& Dohme (UK) Limited, UK), in healthy volunteers in fasted conditions.

Conditions

Viral Infection; COVID-19

Outcome Measures

Primary Outcomes (11)

• Pharmacokinetics - Cmax

  Maximum plasma concentration (Cmax) of β-D-N-4-hydroxycytidine (NHC)

  From 0 to 24 hours (Day 1-2 and Day 8-9)

• Pharmacokinetics - tmax

  Time to reach Cmax (tmax) of NHC

  From 0 to 24 hours (Day 1-2 and Day 8-9)

• Pharmacokinetics - AUC0-t

  Area under the plasma concentration-time curve from time 0 to t (AUC0-t) of NHC

  From 0 to 24 hours (Day 1-2 and Day 8-9)

• Pharmacokinetics - AUC0-inf

  Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of NHC

  From 0 to 24 hours (Day 1-2 and Day 8-9)

• Pharmacokinetics - AUCextr

  Extrapolated AUC of NHC, defined as (AUC0-inf - AUC0-t)/AUC0-inf

  From 0 to 24 hours (Day 1-2 and Day 8-9)

• Pharmacokinetics - t1/2

  Elimination half-life (t1/2) of NHC

  From 0 to 24 hours (Day 1-2 and Day 8-9)

• Pharmacokinetics - kel

  Elimination constant (kel) of NHC

  From 0 to 24 hours (Day 1-2 and Day 8-9)

• Pharmacokinetics - MRT

  Mean residence time (MRT) of NHC

  From 0 to 24 hours (Day 1-2 and Day 8-9)

• Bioequivalence - ratio of Cmax

  Ratio of geometric mean Cmax for NHC after intake of R or T (with 90% confidence intervals)

  From 0 to 24 hours (Day 1-2 and Day 8-9)

• Bioequivalence - ratio of AUC0-t

  Ratio of geometric mean AUC0-t for NHC after intake of R or T (with 90% confidence intervals)

  From 0 to 24 hours (Day 1-2 and Day 8-9)

• Bioequivalence - ratio of AUC0-inf

  Ratio of geometric mean AUC0-inf for NHC after intake of R or T (with 90% confidence intervals)

  From 0 to 24 hours (Day 1-2 and Day 8-9)

Secondary Outcomes (48)

• Safety and Tolerability: adverse event (AE) number and frequency

  From the screening (and signing informed consent form) to Day 14 of the study or to an early termination visit within the time frame of the study (from Day 0 to Day 14)

• Safety and Tolerability: adverse event (AE) characteristics

  From the screening (and signing informed consent form) to Day 14 of the study or to an early termination visit within the time frame of the study (from Day 0 to Day 14)

• Safety and Tolerability: vital signs - systolic blood pressure (SBP)

  Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 14)

• Safety and Tolerability: vital signs - diastolic blood pressure (DBP)

  Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 14)

• Safety and Tolerability: vital signs - respiratory rate (RR)

  Screening, from Day 0 to Day 2, from Day 7 to Day 9, and/or on early termination visit within the time frame of the study (from Day 0 to Day 14)

Study Arms (2)

RT-sequence

OTHER

The volunteers will take 1 capsule (200 mg) of Lagevrio (R), 200 mg capsules (Merck Sharp \& Dohme (UK) Limited, UK) in Period 1, and 1 capsule (200 mg) of Molnupiravir (T), 200 mg capsules (Valenta Pharm, Russia) in Period 2.

Drug: Molnupiravir

TR-sequence

OTHER

The volunteers will take 1 capsule (200 mg) of the drug Molnupiravir (T), capsules, 200 mg (Valenta Pharm JSC, Russia) in Period 1, and 1 capsule (200 mg) of the drug Lagevrio (R), capsules, 200 mg (Merck Sharp \& Dohme (UK) Limited, UK) in Period 2.

Drug: Molnupiravir

Interventions

Molnupiravir DRUG

A single dose of R or T drug in each of 2 periods of the study in fasted conditions

RT-sequence; TR-sequence

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Presence of written consent of the volunteer to participate in the study in accordance with applicable law.
• Healthy male and female caucasian volunteers aged 18 to 45 years (inclusive).
• Verified diagnosis "healthy": no deviations from the reference values of the data of standard clinical, laboratory and instrumental methods of examination.
• Systolic blood pressure (SBP) in the range of 110-130 mmHg; diastolic blood pressure (DBP) is 60-85 mmHg).
• bpm at rest for heart rate (HR).
• breaths/min for respiratory rate (RR).
• to 36.9°C for body temperature.
• Body mass index (BMI) within the range of 18.5 ≤ BMI ≤ 30 kg/m2 with a body weight not less than 45 kg for female and not less than 55 kg for male volunteers.
• The consent of the volunteer (including the partner) to use adequate methods of contraception during the study and 30 days after its completion; for female volunteers - negative blood/urine test result for β-chorionic gonadotropin.
• Volunteers must behave adequately, coherent speech must be observed.

You may not qualify if:

• A history of allergy;
• A history of drug intolerance to the active and/or excipients in the study drugs;
• Chronic diseases of the kidneys, liver, gastrointestinal tract (GIT), cardiovascular, lymphatic, respiratory, nervous, endocrine, musculoskeletal, genitourinary and immune systems, as well as skin, blood and vision;
• History of gastrointestinal surgery (except appendectomy at least 1 year prior to screening);
• Diseases/conditions that in the opinion of the investigator may affect the absorption, distribution, metabolism or excretion of the study drugs (drugs);
• Acute infectious disease less than 4 weeks prior to screening;
• Taking medications that significantly affect hemodynamics and medications that affect liver function (barbiturates, omeprazole, cimetidine, etc.) less than 2 months prior to screening;
• Regularly taking a medicines less than 2 weeks before screening and taking a single medicine less than 7 days before screening;
• Donating blood or plasma less than 3 months before screening;
• Use of hormonal contraceptives (in women) less than 2 months before screening;
• The use of depot injections of any drug less than 3 months before screening;
• Pregnancy or lactation; positive blood/urine β-CGH test for women with preserved reproductive potential;
• Women of preserved reproductive potential with a history of unprotected intercourse within 30 days prior to study drug administration with an unsterilized partner;
• Participation in another clinical trial less than 3 months prior to screening or concurrently with the present study;
• Smoking more than 10 cigarettes per day currently, or a history of smoking the specified number of cigarettes during the 6 months prior to screening; disagreement to abstain from smoking for the duration of the hospital stay;

Sponsors & Collaborators

• Valenta Pharm JSC: lead

Study Sites (1)

Limited Liability Company "Research Center Eco-Safety"

Saint Petersburg, 196143, Russia

Location

MeSH Terms

Conditions

Virus Diseases; COVID-19

Interventions

molnupiravir

Condition Hierarchy (Ancestors)

Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2022
• First Posted: June 9, 2022
• Study Start: April 22, 2022
• Primary Completion: May 17, 2022
• Study Completion: June 2, 2022
• Last Updated: July 27, 2023

Record last verified: 2023-07

Locations

RU (1)