<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03005210</url>
  </required_header>
  <id_info>
    <org_study_id>GRC/1/16/610</org_study_id>
    <nct_id>NCT03005210</nct_id>
  </id_info>
  <brief_title>A Study of Sofosbuvir and Ledipasvir From Magicbuvir Plus 90/400 mg Tablets (Magic Pharma, Egypt) Versus Harvoni 90/400 mg Tablets (Gilead Sciences, USA)</brief_title>
  <official_title>Open Label Randomized, Single Dose, Three Way Three Sequence Two Treatment Partial Replicate Crossover Bioequivalence Study of Sofosbuvir and Ledipasvir From Magicbuvir Plus 90/400 mg Tablets (Magic Pharma, Egypt) Versus Harvoni 90/400 mg Tablets (Gilead Sciences, USA)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genuine Research Center, Egypt</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Magic Pharma, Egypt</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Genuine Research Center, Egypt</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Comparative randomized, single dose, three way three sequence two treatment partial replicate&#xD;
      crossover open-label study to determine the bioequivalence of Sofosbuvir and Ledipasvir from&#xD;
      Magicbuvir Plus 90/400 mg Tablets (Magic Pharma, Egypt) Versus Harvoni 90/400 mg Tablets&#xD;
      (Gilead Sciences, Canada) in Healthy Human Volunteers Under Fed Condition.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Pharmacokinetic Parameters: Cmax, Area under cover (AUC0→t and AUC0→∞ ) Secondary&#xD;
      Pharmacokinetic Parameters: Ke, tmax and t1/2e. ANOVA using 5% significance level for&#xD;
      transformed (with the 90% confidence intervals) and untransformed data of Cmax, AUC0→t and&#xD;
      AUC0→∞ and for untransformed data of Ke, tmax and t1/2e. The confidence intervals of&#xD;
      logarithmically transformed Test/Reference ratios for Cmax, AUC0→t and AUC0→∞ to be within&#xD;
      80.00-125.00%.&#xD;
&#xD;
      A comprehensive final report will be issued upon the completion of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">November 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximal measured plasma concentration (Cmax)</measure>
    <time_frame>Up to 72 hours post dose in each treatment period</time_frame>
    <description>Serial blood samples for determination of study drug will be collected at 0.00, 0.166, 0.33, 0.50, 0.75, 1.00, 1.33, 1.66, 2.00, 2.50, 3.00, 4.00, 6.00, 7.00 , 9.00, 12.00, 24.00, 48.00 and 72.00 hours</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time of the maximum plasma concentration (Tmax)</measure>
    <time_frame>Up to 72 hours post dose in each treatment period</time_frame>
    <description>The amount of time that a drug is present at the maximum concentration in serum</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>T test</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Test drug (Magicbuvir Plus)1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B reference (first dose)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Reference drug (Harvoni) 1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B reference (second dose)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Reference drug (Harvoni) 1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Magicbuvir Plus</intervention_name>
    <description>1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir</description>
    <arm_group_label>T test</arm_group_label>
    <other_name>Harvoni</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Harvoni (fist dose)</intervention_name>
    <description>1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir</description>
    <arm_group_label>B reference (first dose)</arm_group_label>
    <other_name>Harvoni</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Harvoni (second dose)</intervention_name>
    <description>1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir</description>
    <arm_group_label>B reference (second dose)</arm_group_label>
    <other_name>Harvoni</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy male or female, age 18 to 55 years, inclusive.&#xD;
&#xD;
          2. Body weight within 15% of normal range according to the accepted normal values for&#xD;
             body mass index (BMI).&#xD;
&#xD;
          3. Medical demographics without evidence of clinically significant deviation from normal&#xD;
             medical condition.&#xD;
&#xD;
          4. Results of clinical laboratory test are within the normal range or with a deviation&#xD;
             that is not considered clinically significant by principal investigator.&#xD;
&#xD;
          5. Subject does not have allergy to the drugs under investigation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with known allergy to the products tested.&#xD;
&#xD;
          2. Subjects whose values of BMI were outside the accepted normal ranges.&#xD;
&#xD;
          3. Female subjects who were pregnant, nursing or taking birth control pills.&#xD;
&#xD;
          4. Medical demographics with evidence of clinically significant deviation from normal&#xD;
             medical condition.&#xD;
&#xD;
          5. Results of laboratory tests which are clinically significant.&#xD;
&#xD;
          6. Acute infection within one week preceding first study drug administration.&#xD;
&#xD;
          7. History of drug or alcohol abuse.&#xD;
&#xD;
          8. Subject does not agree not to take any prescription or non-prescription drugs within&#xD;
             two weeks before first study drug administration and until the end of the study.&#xD;
&#xD;
          9. Subject is on a special diet (for example subject is vegetarian).&#xD;
&#xD;
         10. Subject does not agree not to consume any beverages or foods containing&#xD;
             methyl-xanthenes e.g. caffeine (coffee, tea, cola, chocolate etc.) 48 hours prior to&#xD;
             the study administration of either study period until donating the last sample in each&#xD;
             respective period.&#xD;
&#xD;
         11. Subject does not agree not to consume any beverages or foods containing grapefruit 7&#xD;
             days prior to first study drug administration until the end of the study.&#xD;
&#xD;
         12. Subject has a history of severe diseases which have direct impact on the study.&#xD;
&#xD;
         13. Participation in a bioequivalence study or in a clinical study within the last 6 weeks&#xD;
             before first study drug administration.&#xD;
&#xD;
         14. Subject intends to be hospitalized within 3 months after first study drug&#xD;
             administration.&#xD;
&#xD;
         15. Subjects who, through completion of this study, would have donated more than 500 ml of&#xD;
             blood in 7 days, or 750 ml of blood in 30 days, 1000 ml in 90 days, 1250 ml in 120&#xD;
             days, 1500 ml in 180 days, 2000 ml in 270 days, 2500 ml of blood in 1 year.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ahmed Elshafeey, Ph.D. Pharma</last_name>
    <role>Study Director</role>
    <affiliation>Genuine Research Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Genuine Research Center GRC</name>
      <address>
        <city>Cairo</city>
        <zip>11757</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <link>
    <url>http://www.ema.europa.eu/ema</url>
    <description>Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) The European Agency for the Evaluation of Medicinal Products (EMEA) May 1997</description>
  </link>
  <link>
    <url>http://www.ema.europa.eu/ema</url>
    <description>Note for Guidance on Clinical Safety Data Management; Definitions And Standards for Expedited Reporting (CPMP/ICH/377/95) The European Agency for the Evaluation of Medicinal Products (EMEA) June 1995.</description>
  </link>
  <reference>
    <citation>Chow SC, Wang H. On sample size calculation in bioequivalence trials. J Pharmacokinet Pharmacodyn. 2001 Apr;28(2):155-69. doi: 10.1023/a:1011503032353. Erratum In: J Pharmacokinet Pharmacodyn. 2002 Feb;29(1):101.</citation>
    <PMID>11381568</PMID>
  </reference>
  <reference>
    <citation>Diletti E, Hauschke D, Steinijans VW. Sample size determination for bioequivalence assessment by means of confidence intervals. Int J Clin Pharmacol Ther Toxicol. 1991 Jan;29(1):1-8.</citation>
    <PMID>2004861</PMID>
  </reference>
  <reference>
    <citation>Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm. 1987 Dec;15(6):657-80. doi: 10.1007/BF01068419.</citation>
    <PMID>3450848</PMID>
  </reference>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 25, 2016</study_first_submitted>
  <study_first_submitted_qc>December 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>December 28, 2016</last_update_submitted>
  <last_update_submitted_qc>December 28, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 29, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ledipasvir, sofosbuvir drug combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03005210
org study id: GRC/1/16/610
nct id: NCT03005210
lead sponsor: 
collaborator: 
has dmc: No
Comparative randomized, single dose, three way three sequence two treatment partial replicate
      crossover open-label study to determine the bioequivalence of Sofosbuvir and Ledipasvir from
      Magicbuvir Plus 90/400 mg Tablets (Magic Pharma, Egypt) Versus Harvoni 90/400 mg Tablets
      (Gilead Sciences, Canada) in Healthy Human Volunteers Under Fed Condition.
Primary Pharmacokinetic Parameters: Cmax, Area under cover (AUC0→t and AUC0→∞ ) Secondary
      Pharmacokinetic Parameters: Ke, tmax and t1/2e. ANOVA using 5% significance level for
      transformed (with the 90% confidence intervals) and untransformed data of Cmax, AUC0→t and
      AUC0→∞ and for untransformed data of Ke, tmax and t1/2e. The confidence intervals of
      logarithmically transformed Test/Reference ratios for Cmax, AUC0→t and AUC0→∞ to be within
      80.00-125.00%.

      A comprehensive final report will be issued upon the completion of the study.
allocation: Randomized
intervention model: Crossover Assignment
masking: None (Open Label)
measure: Maximal measured plasma concentration (Cmax)
time frame: Up to 72 hours post dose in each treatment period
description: Serial blood samples for determination of study drug will be collected at 0.00, 0.166, 0.33, 0.50, 0.75, 1.00, 1.33, 1.66, 2.00, 2.50, 3.00, 4.00, 6.00, 7.00 , 9.00, 12.00, 24.00, 48.00 and 72.00 hours
measure: Time of the maximum plasma concentration (Tmax)
time frame: Up to 72 hours post dose in each treatment period
description: The amount of time that a drug is present at the maximum concentration in serum
arm group label: T test
arm group type: Experimental
description: Test drug (Magicbuvir Plus)1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir
arm group label: B reference (first dose)
arm group type: Active Comparator
description: Reference drug (Harvoni) 1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir
arm group label: B reference (second dose)
arm group type: Active Comparator
description: Reference drug (Harvoni) 1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir
intervention type: Drug
intervention name: Magicbuvir Plus
description: 1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir
arm group label: T test
other name: Harvoni
intervention type: Drug
intervention name: Harvoni (fist dose)
description: 1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir
arm group label: B reference (first dose)
other name: Harvoni
intervention type: Drug
intervention name: Harvoni (second dose)
description: 1 tablet contains 400 mg Sofosbuvir and 90 mg Ledipasvir
arm group label: B reference (second dose)
other name: Harvoni
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ahmed Elshafeey, Ph.D. Pharma
role: Study Director
affiliation: Genuine Research Center
facility: 
country: Egypt
url: http://www.ema.europa.eu/ema
description: Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) The European Agency for the Evaluation of Medicinal Products (EMEA) May 1997
url: http://www.ema.europa.eu/ema
description: Note for Guidance on Clinical Safety Data Management; Definitions And Standards for Expedited Reporting (CPMP/ICH/377/95) The European Agency for the Evaluation of Medicinal Products (EMEA) June 1995.
citation: Chow SC, Wang H. On sample size calculation in bioequivalence trials. J Pharmacokinet Pharmacodyn. 2001 Apr;28(2):155-69. doi: 10.1023/a:1011503032353. Erratum In: J Pharmacokinet Pharmacodyn. 2002 Feb;29(1):101.
PMID: 11381568
citation: Diletti E, Hauschke D, Steinijans VW. Sample size determination for bioequivalence assessment by means of confidence intervals. Int J Clin Pharmacol Ther Toxicol. 1991 Jan;29(1):1-8.
PMID: 2004861
citation: Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm. 1987 Dec;15(6):657-80. doi: 10.1007/BF01068419.
PMID: 3450848
responsible party type: Sponsor
mesh term: Ledipasvir, sofosbuvir drug combination
sharing ipd: Undecided