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CachexiaPhase 1NCT06028321

Study of Comparative Bioavailability and Pharmacokinetics of ACM-001.1) and Pindolol in Healthy Volunteers (HV)

A Phase 1 study testing Part 1 Group 1 Regime A (ACM-001.1), Part 1 Group 2 Regimen C (Pindolol) and Part 2 Group D (Pindolol) in people with Cachexia, run by Actimed Therapeutics Ltd at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 20 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Cachexia
What is being tested?
Part 1 Group 1 Regime A (ACM-001.1), Part 1 Group 2 Regimen C (Pindolol) and Part 2 Group D (Pindolol)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
51 participants
Where
1 siteUnited Kingdom
Study dates
26 Nov 2021to 2 Jun 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy males or non-pregnant, non-lactating healthy females
  • Aged 20 to 45 years inclusive at the time of signing informed consent
  • Body Mass Index (BMI) of 18.0 to 30.0 kg/m2 as measured at screening
  • Weight of 50 to 100 kg at screening

Who cannot join

  • Subjects who had received any investigational medicinal product in a clinical research study within the 90 days prior to Day 1,
  • Subjects for whom pindolol was contraindicated: hypersensitivity to the active substance or to any of its listed excipients.
  • Evidence of current Severe Acute Respiratory Coronavirus 2 infection.
  • History of any drug or alcohol abuse in the past 2 years.
  • Females of childbearing potential who were pregnant or lactating.
  • History of clinically significant cardiovascular disease, Raynaud's disease or phenomenon, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder.
  • Subjects who were found to have mean heart rate less than 50 bpm at rest or mean systolic blood pressure (BP) less than 100 mmHg or mean diastolic heart rate less than 50 mmHg.
  • Subjects who were taking, or had taken, any prescribed or over-the-counter drug or herbal remedies (other than paracetamol, hormonal replacement therapy/hormonal contraception). Pindolol should not be taken in conjunction with agents which inhibit calcium transport.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • Quotient Sciences Ltd

    Ruddington, NG11 9JS

Other trials in United Kingdom

About this study

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)

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.

Conditions
Cachexia
Being tested
Part 1 Group 1 Regime A (ACM-001.1), Part 1 Group 2 Regimen C (Pindolol), Part 2 Group D (Pindolol), Part 2 Group E (ACM-001.1), Part 2 Group F (ACM-001.1 )
Medical subject headings
Cachexia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Part 1 Group 1 Regime A (ACM-001.1)Drug

    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.

  • Part 1 Group 2 Regimen C (Pindolol)Drug

    Drug: Pindolol tablets for oral use.

  • Part 2 Group D (Pindolol)Drug

    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.

  • Part 2 Group E (ACM-001.1)Drug

    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.

  • Part 2 Group F (ACM-001.1 )Drug

    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.

  • Part 2 Group G (ACM-001.1)Drug

    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.

  • Part 1 Group 1 Regimen B (Pindolol)Drug

    Drug: pindolol tablets for oral use. Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B.

  • Part 1 Group 1 Regimen A (Placebo)Other

    Placebo for oral use. Subjects randomised to Regimen A received placebo tablets to match the tablet number received by subjects in Regimen B.

  • Part 2 Group E (Placebo)Other

    Placebo 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.

  • Part 2 Group F (Placebo)Other

    Placebo 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.

  • Part 2 Group G ( Placebo)Other

    Placebo 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.

Study groups in NCT06028321
Study groupRoleWhat they receive
Part 1 Group1 (AB)ExperimentalPart 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.
Receives: Drug: Part 1 Group 1 Regime A (ACM-001.1); Drug: Part 1 Group 1 Regimen B (Pindolol); Other: Part 1 Group 1 Regimen A (Placebo)
Part 1 Group 1 (BA)ExperimentalSubjects 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.
Receives: Drug: Part 1 Group 1 Regime A (ACM-001.1); Drug: Part 1 Group 1 Regimen B (Pindolol); Other: Part 1 Group 1 Regimen A (Placebo)
Part 1 Group 2 (C)ExperimentalSubjects were non-randomised; received regimen C in parallel with Group 1 in a single period. Regimen C = 15 mg pindolol.
Receives: Drug: Part 1 Group 2 Regimen C (Pindolol)
Part 2 Group DExperimentalSubjects received one of the four regimens over a four day treatment period. Regimen D = 20 mg pindolol BID (bis in die) for four days.
Receives: Drug: Part 2 Group D (Pindolol)
Part 2 Group EExperimentalSubjects 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.
Receives: Drug: Part 2 Group E (ACM-001.1); Other: Part 2 Group E (Placebo)
Part 2 Group FExperimentalSubjects 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.
Receives: Drug: Part 2 Group F (ACM-001.1 ); Other: Part 2 Group F (Placebo)
Part 2 Group GExperimentalSubjects 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.
Receives: Drug: Part 2 Group G (ACM-001.1); Other: Part 2 Group G ( Placebo)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1 Composite of PK parameters following single doses

    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].

    Measured: Up to 5 days

  2. Part 1 PK parameters following single doses

    Comparative bioavailability of S- pindolol and pindolol include:maximum observed concentration (Cmax)

    Measured: Up to 5 days

  3. Part 1 PK parameters following single doses

    Comparative bioavailability of S- pindolol and pindolol include:time of occurrence of Cmax (Tmax)

    Measured: Up to 5 days

  4. PK parameters following single doses

    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]).

    Measured: Up to 5 days

  5. PK parameters following single doses

    Comparative PK parameters of S- pindolol and racemic pindolol include: maximum observed concentration (Cmax)

    Measured: Up to 5 days

  6. PK parameters following single doses

    Comparative PK parameters of S- pindolol and racemic pindolol include: t time of occurrence of Cmax (Tmax)

    Measured: Up to 5 days

  7. Stoichiometric dose relationship measured using PK parameters following single doses

    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])

    Measured: Up to 5 days

  8. Stoichiometric dose relationship measured using PK parameters following single doses

    PK parameters of S- pindolol and racemic pindolol include: maximum observed concentration (Cmax).

    Measured: Up to 5 days

  9. Part 2 Composite of PK parameters following multiple doses in plasma

    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])

    Measured: Up to 6 days

  10. Part 2 Composite of PK parameters following multiple doses in plasma

    PK parameters of S- pindolol/racemic pindolol: Maximum observed concentration (Cmax),

    Measured: Up to 6 days

  11. Part 2 Composite of PK parameters following multiple doses in plasma

    PK parameters of S- pindolol/racemic pindolol: Time to first occurrence of Cmax from plasma concentration-time data(Tmax).

    Measured: Up to 6 days

  12. Pharmacodynamics of ACM-001.1: Cardiovascular vital parameter- heart rate

    Heart rate (beats per minute)

    Measured: Up to 6 days

  13. Cardiovascular vital parameter- blood pressure

    Systolic blood pressure (mmHG) and diastolic blood pressure (mmHG)

    Measured: Up to 6 days

  14. Serum biomarker- DHEA/Cortisol

    Dehydroepiandrosterone (DHEA)/Cortisol (ng/mL). Serum concentrations were determined using validated analytical method.

    Measured: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours

  15. Serum biomarker- Myostatin

    Myostatin (pg/mL).Serum concentrations were determined using validated analytical method.

    Measured: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.

  16. Serum biomarker- Folistatin

    Folistatin (pg/mL).Serum concentrations were determined using validated analytical method.

    Measured: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.

  17. Serum biomarker-IGF1

    Insulin-like growth factor (IGF)1 (pg/mL).Serum concentrations were determined using validated analytical method.

    Measured: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.

  18. Serum biomarker - (Type 3 procollagen peptide) PIIINP

    PIIINP (pg/mL).Serum concentrations were determined using validated analytical method.

    Measured: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.

  19. Serum biomarker - monokine-induced by gamma interferon (MIG/CXL9) Leptin

    Leptin (pg/mL).Serum concentrations were determined using validated analytical method.

    Measured: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.

  20. Serum biomarker - epithelial neutrophil activating peptide 78 (ENA78)

    ENA78 (pg/mL).Serum concentrations were determined using validated analytical method.

    Measured: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.

  21. Serum biomarker - Ghrelin

    Ghrelin (pg/mL).Serum concentrations were determined using validated analytical method.

    Measured: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.

  22. Serum biomarker - Growth Hormone Receptor Hormone

    Growth Hormone Receptor Hormone (ng/mL).Serum concentrations were determined using validated analytical method.

    Measured: Day 1 at pre-dose. Day 4 at pre-dose, 1.5 hours.

  23. Serum biomarker - Somatostatin

    Somatostatin (pg/mL).Serum concentrations were determined using validated analytical method.

    Measured: Day 1 at pre-dose (baseline). Day 4 at pre-dose, 1.5 hours.

Secondary outcomes (6)
  1. Part 1 Composite PK parameters in urine following single doses

    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)

    Measured: Up to 5 days

  2. Part 2 Composite PK parameters in urine following multiple doses and pindolol

    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)

    Measured: Up to 7 days

  3. Part 1 and Part 2 Analysis of S-pindolol and R-pindolol concentrations in plasma for any in vivo conversion

    Plasma concentrations were determined using validated analytical methods.

    Measured: Up to 4 days

  4. Part 1 Number of participants with adverse events following single doses as a measure of safety and tolerability

    AEs will be collected from provision of written informed consent until discharge at the follow-up contact.

    Measured: From screening: day -28 to follow up call on day 8 (part 1), up to 36 days.

  5. Part 2 Number of participants with adverse events following single doses as a measure of safety and tolerability

    AEs will be collected from provision of written informed consent until discharge at the follow-up contact

    Measured: From screening: day -28 to follow up call on day 11 (part 2), up to 39 days.

  6. Part 2 only - Pulmonary function test

    Forced expiratory spirometry to determine parameters FEV1, FVC, FEV1/FVC

    Measured: Up to 32 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2023
  2. Study start26 Nov 2021
  3. Primary completion2 Jun 2022
  4. Study completion2 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
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.
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06028321
Sponsor's protocol ID
ACM-2021-1-CT
Other IDs
QSC205141
Status last verified
Oct 2023
First submitted
6 Jul 2023
Last updated
10 Oct 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Misselwitz F, Henderson D, Menakuru SR, Morten E, Roe C, Whitaker G, Wohlfeil S, McDermott J. Pharmacokinetics, Pharmacodynamics and Bioavailability of ACM-001.1 (S-Pindolol Benzoate) in Healthy Volunteers. J Cachexia Sarcopenia Muscle. 2025 Feb;16(1):e13651. doi: 10.1002/jcsm.13651. Epub 2024 Dec 12.

    PubMed 39665235

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Part 1 Group 1 Regime A (ACM-001.1), Part 1 Group 2 Regimen C (Pindolol) and Part 2 Group D (Pindolol) in people with Cachexia, run by Actimed Therapeutics Ltd at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 Composite of PK parameters following single doses (time frame: Up to 5 days). The study lists 23 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06028321, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2023.

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