xml: <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/NCT06028321</url>
    </required_header>
    <id_info>
      <org_study_id>ACM-2021-1-CT</org_study_id>
      <secondary_id>QSC205141</secondary_id>
      <nct_id>NCT06028321</nct_id>
    </id_info>
    <brief_title>Study of Comparative Bioavailability and Pharmacokinetics of ACM-001.1) and Pindolol in Healthy Volunteers (HV)</brief_title>
    <official_title>Two Part Study to Assess Comparative Bioavailability, Pharmacokinetics of a Single Dose of ACM-001.1, Two Single Doses of Pindolol (Part1) Followed by Evaluation of Steady State Pharmacokinetics, Pharmacodynamics of ACM-001.1 in HV (Part2)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Actimed Therapeutics Ltd</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Quotient Sciences</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Actimed Therapeutics Ltd</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The aim of this early phase two-part study was to compare the bioavailability (BA)&#xD;
        pharmacokinetics (PK) and pharmacodynamics (PD) of racemic pindolol with the benzoate salt of&#xD;
        the S-enantiomer of pindolol (ACM-001.1) and provide safety information. A total of 51&#xD;
        healthy male and female subjects were enrolled, and 48 healthy subjects completed the study.&#xD;
  &#xD;
        Part 1 consisted of two Groups to compare BA and PK, Group 1 received two treatment sequences&#xD;
        of a single dose of ACM-001.1 versus racemic pindolol; Group 2 ran in parallel with Group 1&#xD;
        and assessed the PK of a single dose of racemic pindolol in a single period.&#xD;
  &#xD;
        Part 2 consisted of four groups, to evaluate the steady state PK and PD of ACM-001.1 with&#xD;
        multiple ascending doses over 4 days.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">November 26, 2021</start_date>
    <completion_date type="Actual">June 2, 2022</completion_date>
    <primary_completion_date type="Actual">June 2, 2022</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>
      <intervention_model_description>Part 1: part - blinded, part randomized, partial cross- over study. Group 1: double - blinded and randomized to two treatment sequences in a two period cross- over.&#xD;
  Group 2: open label, non-randomized and in parallel with Group 1. Part 2: single-blind (subject blinded), randomized, parallel-group.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
      <masking_description>Part 2 was single - blind study (subject blinded). Masking was not triple for all parts of the study or all arms.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Part 1 Composite of PK parameters following single doses</measure>
      <time_frame>Up to 5 days</time_frame>
      <description>Comparative bioavailability of S- pindolol and pindolol include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinite].</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 1 PK parameters following single doses</measure>
      <time_frame>Up to 5 days</time_frame>
      <description>Comparative bioavailability of S- pindolol and pindolol include:maximum observed concentration (Cmax)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 1 PK parameters following single doses</measure>
      <time_frame>Up to 5 days</time_frame>
      <description>Comparative bioavailability of S- pindolol and pindolol include:time of occurrence of Cmax (Tmax)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>PK parameters following single doses</measure>
      <time_frame>Up to 5 days</time_frame>
      <description>Comparative PK parameters of S- pindolol and racemic pindolol include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinite]).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>PK parameters following single doses</measure>
      <time_frame>Up to 5 days</time_frame>
      <description>Comparative PK parameters of S- pindolol and racemic pindolol include: maximum observed concentration (Cmax)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>PK parameters following single doses</measure>
      <time_frame>Up to 5 days</time_frame>
      <description>Comparative PK parameters of S- pindolol and racemic pindolol include: t time of occurrence of Cmax (Tmax)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Stoichiometric dose relationship measured using PK parameters following single doses</measure>
      <time_frame>Up to 5 days</time_frame>
      <description>PK parameters of S- pindolol and racemic pindolol include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinite])</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Stoichiometric dose relationship measured using PK parameters following single doses</measure>
      <time_frame>Up to 5 days</time_frame>
      <description>PK parameters of S- pindolol and racemic pindolol include: maximum observed concentration (Cmax).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 2 Composite of PK parameters following multiple doses in plasma</measure>
      <time_frame>Up to 6 days</time_frame>
      <description>PK parameters of S- pindolol/racemic pindolol:Area under the curve for interval between doses (tau) (AUC(0 tau);Area under the concentration-time curve from time zero (pre-dose) to last time of measurable concentration (AUC[0-t])</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 2 Composite of PK parameters following multiple doses in plasma</measure>
      <time_frame>Up to 6 days</time_frame>
      <description>PK parameters of S- pindolol/racemic pindolol: Maximum observed concentration (Cmax),</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 2 Composite of PK parameters following multiple doses in plasma</measure>
      <time_frame>Up to 6 days</time_frame>
      <description>PK parameters of S- pindolol/racemic pindolol: Time to first occurrence of Cmax from plasma concentration-time data(Tmax).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Pharmacodynamics of ACM-001.1: Cardiovascular vital parameter- heart rate</measure>
      <time_frame>Up to 6 days</time_frame>
      <description>Heart rate (beats per minute)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Cardiovascular vital parameter- blood pressure</measure>
      <time_frame>Up to 6 days</time_frame>
      <description>Systolic blood pressure (mmHG) and diastolic blood pressure (mmHG)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serum biomarker- DHEA/Cortisol</measure>
      <time_frame>Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours</time_frame>
      <description>Dehydroepiandrosterone (DHEA)/Cortisol (ng/mL). Serum concentrations were determined using validated analytical method.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serum biomarker- Myostatin</measure>
      <time_frame>Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.</time_frame>
      <description>Myostatin (pg/mL).Serum concentrations were determined using validated analytical method.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serum biomarker- Folistatin</measure>
      <time_frame>Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.</time_frame>
      <description>Folistatin (pg/mL).Serum concentrations were determined using validated analytical method.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serum biomarker-IGF1</measure>
      <time_frame>Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.</time_frame>
      <description>Insulin-like growth factor (IGF)1 (pg/mL).Serum concentrations were determined using validated analytical method.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serum biomarker - (Type 3 procollagen peptide) PIIINP</measure>
      <time_frame>Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.</time_frame>
      <description>PIIINP (pg/mL).Serum concentrations were determined using validated analytical method.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serum biomarker - monokine-induced by gamma interferon (MIG/CXL9) Leptin</measure>
      <time_frame>Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.</time_frame>
      <description>Leptin (pg/mL).Serum concentrations were determined using validated analytical method.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serum biomarker - epithelial neutrophil activating peptide 78 (ENA78)</measure>
      <time_frame>Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.</time_frame>
      <description>ENA78 (pg/mL).Serum concentrations were determined using validated analytical method.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serum biomarker - Ghrelin</measure>
      <time_frame>Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.</time_frame>
      <description>Ghrelin (pg/mL).Serum concentrations were determined using validated analytical method.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serum biomarker - Growth Hormone Receptor Hormone</measure>
      <time_frame>Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.</time_frame>
      <description>Growth Hormone Receptor Hormone (ng/mL).Serum concentrations were determined using validated analytical method.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serum biomarker - Somatostatin</measure>
      <time_frame>Day 1 at pre-dose (baseline). Day 4 at pre-dose, 1.5 hours.</time_frame>
      <description>Somatostatin (pg/mL).Serum concentrations were determined using validated analytical method.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Part 1 Composite PK parameters in urine following single doses</measure>
      <time_frame>Up to 5 days</time_frame>
      <description>PK parameters of S-pindolol, R-pindolol and pindolol: Amount excreted (Ae), Cumulative amount excreted (CumAe), Fraction of dose excreted (%Ae) and Cumulative fraction of dose excreted (%CumAe)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2 Composite PK parameters in urine following multiple doses and pindolol</measure>
      <time_frame>Up to 7 days</time_frame>
      <description>PK parameters of S-pindolol, R-pindolol and pindolol: Amount excreted (Ae), Cumulative amount excreted (CumAe), Fraction of dose excreted (%Ae) and Cumulative fraction of dose excreted (%CumAe)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1 and Part 2 Analysis of S-pindolol and R-pindolol concentrations in plasma for any in vivo conversion</measure>
      <time_frame>Up to 4 days</time_frame>
      <description>Plasma concentrations were determined using validated analytical methods.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1 Number of participants with adverse events following single doses as a measure of safety and tolerability</measure>
      <time_frame>From screening: day -28 to follow up call day 8 (part 1), up to 36 days</time_frame>
      <description>AEs will be collected from provision of written informed consent until discharge at the follow-up contact.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2 Number of participants with adverse events following single doses as a measure of safety and tolerability</measure>
      <time_frame>From screening: day -28 to follow up call day up to 11 (part 2), up to 39 days</time_frame>
      <description>AEs will be collected from provision of written informed consent until discharge at the follow-up contact</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2 only - Pulmonary function test</measure>
      <time_frame>Up to 32 days</time_frame>
      <description>Forced expiratory spirometry to determine parameters FEV1, FVC, FEV1/FVC</description>
    </secondary_outcome>
    <number_of_arms>7</number_of_arms>
    <enrollment type="Actual">51</enrollment>
    <condition>Cachexia</condition>
    <arm_group>
      <arm_group_label>Part 1 Group1 (AB)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part 1 Group1 Subjects were randomised to two treatment regimens (A and B) and received treatment sequence AB in a 2-period cross over.&#xD;
  Regimen A = 15 mg ACM-001.1 and matching placebo. Regimen B = 30 mg pindolol.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 1 Group 1 (BA)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects were randomised to two treatment regimens (A and B) and received treatment sequence BA in a 2-period cross over.&#xD;
  Regimen B = 30 mg pindolol. Regimen A = 15 mg ACM-001.1 and matching placebo.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 1 Group 2 (C)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects were non-randomised; received regimen C in parallel with Group 1 in a single period.&#xD;
  Regimen C = 15 mg pindolol.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 2 Group D</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects received one of the four regimens over a four day treatment period. Regimen D = 20 mg pindolol BID (bis in die) for four days.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 2 Group E</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects received one of the four regimens over a four day treatment period. Regimen E = 5 mg ACM-001.1 and placebo BID for four days.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 2 Group F</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects received one of the four regimens over a four day treatment period. Regimen F = 10 mg ACM-001.1 and placebo BID for four days.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 2 Group G</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects received one of the four regimens over a four day treatment period. Regimen G = 15 mg ACM-001.1 and placebo BID for four days.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Part 1 Group 1 (ACM-001.1and Pindolol and Placebo)</intervention_name>
      <description>Drug: ACM-001.1 immediate release tablets for oral use and matching placebo, and pindolol tablets for oral use.&#xD;
  Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B.</description>
      <arm_group_label>Part 1 Group 1 (BA)</arm_group_label>
      <arm_group_label>Part 1 Group1 (AB)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Part 1 Group 2 (Pindolol)</intervention_name>
      <description>Drug: Pindolol tablets for oral use.</description>
      <arm_group_label>Part 1 Group 2 (C)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Part 2 Group D (Pindolol)</intervention_name>
      <description>Drug: Pindolol tablets for oral use. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.</description>
      <arm_group_label>Part 2 Group D</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Part 2 Group E (ACM-001.1 and Placebo)</intervention_name>
      <description>Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.</description>
      <arm_group_label>Part 2 Group E</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Part 2 Group F (ACM-001.1 and Placebo)</intervention_name>
      <description>Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.</description>
      <arm_group_label>Part 2 Group F</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Part 2 Group G (ACM-001.1 and Placebo)</intervention_name>
      <description>Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.</description>
      <arm_group_label>Part 2 Group G</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Healthy males or non-pregnant, non-lactating healthy females&#xD;
  &#xD;
            -  Aged 20 to 45 years inclusive at the time of signing informed consent&#xD;
  &#xD;
            -  Body Mass Index (BMI) of 18.0 to 30.0 kg/m2 as measured at screening&#xD;
  &#xD;
            -  Weight of 50 to 100 kg at screening&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Subjects who had received any investigational medicinal product in a clinical research&#xD;
               study within the 90 days prior to Day 1,&#xD;
  &#xD;
            -  Subjects for whom pindolol was contraindicated: hypersensitivity to the active&#xD;
               substance or to any of its listed excipients.&#xD;
  &#xD;
            -  Evidence of current Severe Acute Respiratory Coronavirus 2 infection.&#xD;
  &#xD;
            -  History of any drug or alcohol abuse in the past 2 years.&#xD;
  &#xD;
            -  Females of childbearing potential who were pregnant or lactating.&#xD;
  &#xD;
            -  History of clinically significant cardiovascular disease, Raynaud's disease or&#xD;
               phenomenon, renal, hepatic, dermatological, chronic respiratory or gastrointestinal&#xD;
               disease, neurological or psychiatric disorder.&#xD;
  &#xD;
            -  Subjects who were found to have mean heart rate less than 50 bpm at rest or mean&#xD;
               systolic blood pressure (BP) less than 100 mmHg or mean diastolic heart rate less than&#xD;
               50 mmHg.&#xD;
  &#xD;
            -  Subjects who were taking, or had taken, any prescribed or over-the-counter drug or&#xD;
               herbal remedies (other than paracetamol, hormonal replacement therapy/hormonal&#xD;
               contraception). Pindolol should not be taken in conjunction with agents which inhibit&#xD;
               calcium transport.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>20 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Quotient Sciences Ltd</name>
        <address>
          <city>Ruddington</city>
          <zip>NG11 9JS</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 6, 2023</study_first_submitted>
    <study_first_submitted_qc>August 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 8, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cachexia</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pindolol</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06028321
  org study id: ACM-2021-1-CT
  secondary id: QSC205141
  nct id: NCT06028321
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  The aim of this early phase two-part study was to compare the bioavailability (BA)
        pharmacokinetics (PK) and pharmacodynamics (PD) of racemic pindolol with the benzoate salt of
        the S-enantiomer of pindolol (ACM-001.1) and provide safety information. A total of 51
        healthy male and female subjects were enrolled, and 48 healthy subjects completed the study.
  
        Part 1 consisted of two Groups to compare BA and PK, Group 1 received two treatment sequences
        of a single dose of ACM-001.1 versus racemic pindolol; Group 2 ran in parallel with Group 1
        and assessed the PK of a single dose of racemic pindolol in a single period.
  
        Part 2 consisted of four groups, to evaluate the steady state PK and PD of ACM-001.1 with
        multiple ascending doses over 4 days.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: Part 1: part - blinded, part randomized, partial cross- over study. Group 1: double - blinded and randomized to two treatment sequences in a two period cross- over.
  Group 2: open label, non-randomized and in parallel with Group 1. Part 2: single-blind (subject blinded), randomized, parallel-group.
  primary purpose: Treatment
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  masking description: Part 2 was single - blind study (subject blinded). Masking was not triple for all parts of the study or all arms.
  measure: Part 1 Composite of PK parameters following single doses
  time frame: Up to 5 days
  description: Comparative bioavailability of S- pindolol and pindolol include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinite].
  measure: Part 1 PK parameters following single doses
  time frame: Up to 5 days
  description: Comparative bioavailability of S- pindolol and pindolol include:maximum observed concentration (Cmax)
  measure: Part 1 PK parameters following single doses
  time frame: Up to 5 days
  description: Comparative bioavailability of S- pindolol and pindolol include:time of occurrence of Cmax (Tmax)
  measure: PK parameters following single doses
  time frame: Up to 5 days
  description: Comparative PK parameters of S- pindolol and racemic pindolol include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinite]).
  measure: PK parameters following single doses
  time frame: Up to 5 days
  description: Comparative PK parameters of S- pindolol and racemic pindolol include: maximum observed concentration (Cmax)
  measure: PK parameters following single doses
  time frame: Up to 5 days
  description: Comparative PK parameters of S- pindolol and racemic pindolol include: t time of occurrence of Cmax (Tmax)
  measure: Stoichiometric dose relationship measured using PK parameters following single doses
  time frame: Up to 5 days
  description: PK parameters of S- pindolol and racemic pindolol include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinite])
  measure: Stoichiometric dose relationship measured using PK parameters following single doses
  time frame: Up to 5 days
  description: PK parameters of S- pindolol and racemic pindolol include: maximum observed concentration (Cmax).
  measure: Part 2 Composite of PK parameters following multiple doses in plasma
  time frame: Up to 6 days
  description: PK parameters of S- pindolol/racemic pindolol:Area under the curve for interval between doses (tau) (AUC(0 tau);Area under the concentration-time curve from time zero (pre-dose) to last time of measurable concentration (AUC[0-t])
  measure: Part 2 Composite of PK parameters following multiple doses in plasma
  time frame: Up to 6 days
  description: PK parameters of S- pindolol/racemic pindolol: Maximum observed concentration (Cmax),
  measure: Part 2 Composite of PK parameters following multiple doses in plasma
  time frame: Up to 6 days
  description: PK parameters of S- pindolol/racemic pindolol: Time to first occurrence of Cmax from plasma concentration-time data(Tmax).
  measure: Pharmacodynamics of ACM-001.1: Cardiovascular vital parameter- heart rate
  time frame: Up to 6 days
  description: Heart rate (beats per minute)
  measure: Cardiovascular vital parameter- blood pressure
  time frame: Up to 6 days
  description: Systolic blood pressure (mmHG) and diastolic blood pressure (mmHG)
  measure: Serum biomarker- DHEA/Cortisol
  time frame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours
  description: Dehydroepiandrosterone (DHEA)/Cortisol (ng/mL). Serum concentrations were determined using validated analytical method.
  measure: Serum biomarker- Myostatin
  time frame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
  description: Myostatin (pg/mL).Serum concentrations were determined using validated analytical method.
  measure: Serum biomarker- Folistatin
  time frame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
  description: Folistatin (pg/mL).Serum concentrations were determined using validated analytical method.
  measure: Serum biomarker-IGF1
  time frame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
  description: Insulin-like growth factor (IGF)1 (pg/mL).Serum concentrations were determined using validated analytical method.
  measure: Serum biomarker - (Type 3 procollagen peptide) PIIINP
  time frame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
  description: PIIINP (pg/mL).Serum concentrations were determined using validated analytical method.
  measure: Serum biomarker - monokine-induced by gamma interferon (MIG/CXL9) Leptin
  time frame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
  description: Leptin (pg/mL).Serum concentrations were determined using validated analytical method.
  measure: Serum biomarker - epithelial neutrophil activating peptide 78 (ENA78)
  time frame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
  description: ENA78 (pg/mL).Serum concentrations were determined using validated analytical method.
  measure: Serum biomarker - Ghrelin
  time frame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
  description: Ghrelin (pg/mL).Serum concentrations were determined using validated analytical method.
  measure: Serum biomarker - Growth Hormone Receptor Hormone
  time frame: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.
  description: Growth Hormone Receptor Hormone (ng/mL).Serum concentrations were determined using validated analytical method.
  measure: Serum biomarker - Somatostatin
  time frame: Day 1 at pre-dose (baseline). Day 4 at pre-dose, 1.5 hours.
  description: Somatostatin (pg/mL).Serum concentrations were determined using validated analytical method.
  measure: Part 1 Composite PK parameters in urine following single doses
  time frame: Up to 5 days
  description: PK parameters of S-pindolol, R-pindolol and pindolol: Amount excreted (Ae), Cumulative amount excreted (CumAe), Fraction of dose excreted (%Ae) and Cumulative fraction of dose excreted (%CumAe)
  measure: Part 2 Composite PK parameters in urine following multiple doses and pindolol
  time frame: Up to 7 days
  description: PK parameters of S-pindolol, R-pindolol and pindolol: Amount excreted (Ae), Cumulative amount excreted (CumAe), Fraction of dose excreted (%Ae) and Cumulative fraction of dose excreted (%CumAe)
  measure: Part 1 and Part 2 Analysis of S-pindolol and R-pindolol concentrations in plasma for any in vivo conversion
  time frame: Up to 4 days
  description: Plasma concentrations were determined using validated analytical methods.
  measure: Part 1 Number of participants with adverse events following single doses as a measure of safety and tolerability
  time frame: From screening: day -28 to follow up call day 8 (part 1), up to 36 days
  description: AEs will be collected from provision of written informed consent until discharge at the follow-up contact.
  measure: Part 2 Number of participants with adverse events following single doses as a measure of safety and tolerability
  time frame: From screening: day -28 to follow up call day up to 11 (part 2), up to 39 days
  description: AEs will be collected from provision of written informed consent until discharge at the follow-up contact
  measure: Part 2 only - Pulmonary function test
  time frame: Up to 32 days
  description: Forced expiratory spirometry to determine parameters FEV1, FVC, FEV1/FVC
  arm group label: Part 1 Group1 (AB)
  arm group type: Experimental
  description: Part 1 Group1 Subjects were randomised to two treatment regimens (A and B) and received treatment sequence AB in a 2-period cross over.
  Regimen A = 15 mg ACM-001.1 and matching placebo. Regimen B = 30 mg pindolol.
  arm group label: Part 1 Group 1 (BA)
  arm group type: Experimental
  description: Subjects were randomised to two treatment regimens (A and B) and received treatment sequence BA in a 2-period cross over.
  Regimen B = 30 mg pindolol. Regimen A = 15 mg ACM-001.1 and matching placebo.
  arm group label: Part 1 Group 2 (C)
  arm group type: Experimental
  description: Subjects were non-randomised; received regimen C in parallel with Group 1 in a single period.
  Regimen C = 15 mg pindolol.
  arm group label: Part 2 Group D
  arm group type: Experimental
  description: Subjects received one of the four regimens over a four day treatment period. Regimen D = 20 mg pindolol BID (bis in die) for four days.
  arm group label: Part 2 Group E
  arm group type: Experimental
  description: Subjects received one of the four regimens over a four day treatment period. Regimen E = 5 mg ACM-001.1 and placebo BID for four days.
  arm group label: Part 2 Group F
  arm group type: Experimental
  description: Subjects received one of the four regimens over a four day treatment period. Regimen F = 10 mg ACM-001.1 and placebo BID for four days.
  arm group label: Part 2 Group G
  arm group type: Experimental
  description: Subjects received one of the four regimens over a four day treatment period. Regimen G = 15 mg ACM-001.1 and placebo BID for four days.
  intervention type: Drug
  intervention name: Part 1 Group 1 (ACM-001.1and Pindolol and Placebo)
  description: Drug: ACM-001.1 immediate release tablets for oral use and matching placebo, and pindolol tablets for oral use.
  Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B.
  arm group label: Part 1 Group 1 (BA)
  arm group label: Part 1 Group1 (AB)
  intervention type: Drug
  intervention name: Part 1 Group 2 (Pindolol)
  description: Drug: Pindolol tablets for oral use.
  arm group label: Part 1 Group 2 (C)
  intervention type: Drug
  intervention name: Part 2 Group D (Pindolol)
  description: Drug: Pindolol tablets for oral use. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.
  arm group label: Part 2 Group D
  intervention type: Drug
  intervention name: Part 2 Group E (ACM-001.1 and Placebo)
  description: Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.
  arm group label: Part 2 Group E
  intervention type: Drug
  intervention name: Part 2 Group F (ACM-001.1 and Placebo)
  description: Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.
  arm group label: Part 2 Group F
  intervention type: Drug
  intervention name: Part 2 Group G (ACM-001.1 and Placebo)
  description: Drug: ACM-001.1 immediate release tablets for oral use and matching placebo. Subjects were dosed over a four day treatment period twice daily. Subjects receiving ACM-001.1 in regimens E, F and G also received placebo tablets to match the tablet number received by subjects receiving pindolol in Regimen D.
  arm group label: Part 2 Group G
  criteria: 
  gender: All
  minimum age: 20 Years
  maximum age: 45 Years
  healthy volunteers: Accepts Healthy Volunteers
  facility: 
  country: United Kingdom
  responsible party type: Sponsor
  mesh term: Cachexia
  mesh term: Pindolol
  sharing ipd: No