CASK0120

Cassella-med GmbH & Co. KG

Gereonsmühlengasse 1, Cologne, Germany, 50670

Global Scientific Development & Clinical Operations, Cassella-med GmbH & Co. KG, +49 2211652565, clinical.operations@klosterfrau.de

Global Scientific Development & Clinical Operations, Cassella-med GmbH & Co. KG, +49 2211652565, clinical.operations@klosterfrau.de

No

No

No

Final

07 Jul 2021

Yes

19 May 2021

Yes

19 May 2021

No

The objective of this clinical trial is to investigate the relation between timing of treatment onset with cineole and course of a common cold with or without acute bronchitis.

A SARS-CoV-2 test was performed at visit 2 to exclude Covid-19 positiv patients from participation at the study. Despite this, in the event of fever and / or profound / protracted pain the patients were allowed to use rescue medication (paracetamol 500 mg).

17 Sep 2020

No

No

Germany: 522

522

522

0

0

0

0

0

0

505

17

0

Screening phase

Not applicable

No investigational medicinal product assigned in this arm

Illness phase

Not applicable

No investigational medicinal product assigned in this arm

Treatment phase

Not applicable

Yes

Soledum® forte capsules

R05CA13

German original name: Soledum® Kapseln forte

Gastro-resistant capsule, soft

Oral use

The IMP will be administered at home three times a day (morning, noon, evening, t.i.d.: 3x1 capsules). Treatment starts on the day of Visit 2 (Day 1) at the trial site and ends on the day of Visit 4 (Day 15±2) at home. Subjects, who recover from common cold before Visit 4, may terminate the administration of the IMP, once the first 10 WURSS-11 questions were rated by the subject “0” on two consecutive assessments in the eDiary. On Day 1 (start of treatment), the IMP will be administered once (1x1 capsule), twice (2x1 capsule) or three times (3x1 capsule) by the subject depending on the time of Visit 2. On the day of Visit 4 (Day 15±2), the IMP will only be administered once in the morning (1x1 capsule, last dose). IMP has to be swallowed unchewed with sufficient fluid (preferably one glass of water [200 mL]), but no hot beverage, approximately half an hour before a meal. Subjects with a sensitive stomach are recommended to take the IMP during their regular meals.

Soledum® forte capsules

R05CA13

German original name: Soledum® Kapseln forte

Gastro-resistant capsule, soft

Oral use

The IMP will be administered at home three times a day (morning, noon, evening, t.i.d.: 3x1 capsules). Treatment starts on the day of Visit 2 (Day 1) at the trial site and ends on the day of Visit 4 (Day 15±2) at home. Subjects, who recover from common cold before Visit 4, may terminate the administration of the IMP, once the first 10 WURSS-11 questions were rated by the subject “0” on two consecutive assessments in the eDiary. On Day 1 (start of treatment), the IMP will be administered once (1x1 capsule), twice (2x1 capsule) or three times (3x1 capsule) by the subject depending on the time of Visit 2. On the day of Visit 4 (Day 15±2), the IMP will only be administered once in the morning (1x1 capsule, last dose). IMP has to be swallowed unchewed with sufficient fluid (preferably one glass of water [200 mL]), but no hot beverage, approximately half an hour before a meal. Subjects with a sensitive stomach are recommended to take the IMP during their regular meals.

Soledum® forte capsules

R05CA13

German original name: Soledum® Kapseln forte

Gastro-resistant capsule, soft

Oral use

The IMP will be administered at home three times a day (morning, noon, evening, t.i.d.: 3x1 capsules). Treatment starts on the day of Visit 2 (Day 1) at the trial site and ends on the day of Visit 4 (Day 15±2) at home. Subjects, who recover from common cold before Visit 4, may terminate the administration of the IMP, once the first 10 WURSS-11 questions were rated by the subject “0” on two consecutive assessments in the eDiary. On Day 1 (start of treatment), the IMP will be administered once (1x1 capsule), twice (2x1 capsule) or three times (3x1 capsule) by the subject depending on the time of Visit 2. On the day of Visit 4 (Day 15±2), the IMP will only be administered once in the morning (1x1 capsule, last dose). IMP has to be swallowed unchewed with sufficient fluid (preferably one glass of water [200 mL]), but no hot beverage, approximately half an hour before a meal. Subjects with a sensitive stomach are recommended to take the IMP during their regular meals.

≤12 h

>12 to 24 h

>24 h

mITT

Modified intention-to-treat set (mITT) comprised all subjects: • who received at least 4 IMP doses within the first 4 days after Visit 2 with maximum one day without treatment; • who provided at least 5 valid WURSS-11 assessments within the first 7 days after symptom onset with a maximum of 2 days without assessment; • without intake of antibiotics after start of IMP treatment due to symptoms associated with upper respiratory tract infections. The mITT was used for the identification of potential confounders and for the evaluation of primary and secondary endpoints in a more “real-life” setting.

SAF

Safety Set (SAF) included all subjects, who received at least one dose of the IMP. The SAF was used for analysis of safety and tolerability.

Screening Phase

Onset of symptoms

≤12 h

>12 to 24 h

>24 h

mITT

Modified intention-to-treat set (mITT) comprised all subjects: • who received at least 4 IMP doses within the first 4 days after Visit 2 with maximum one day without treatment; • who provided at least 5 valid WURSS-11 assessments within the first 7 days after symptom onset with a maximum of 2 days without assessment; • without intake of antibiotics after start of IMP treatment due to symptoms associated with upper respiratory tract infections. The mITT was used for the identification of potential confounders and for the evaluation of primary and secondary endpoints in a more “real-life” setting.

SAF

Safety Set (SAF) included all subjects, who received at least one dose of the IMP. The SAF was used for analysis of safety and tolerability.

The primary efficacy endpoint was the Area under the curve global symptom severity (AUC-WURSS) using the primary efficacy variable subject-reported outcome WURSS-11. The derivation of AUC-WURSS was based on mean daily total WURSS-11 scores, which were derived by averaging evening assessment of considered symptom day and morning assessment of the subsequent day separately for each item. If only one of both assessments was available, this assessment was used as mean item score for a symptom day. The mean item scores for questions 2 to 10 (daily single item scores) were then summed up to the mean total score of a day. Imputation of missing data was performed up to (estimated) day of recovery.

Primary

The mean daily total scores (imputed) were summed up from Symptom Day 1 to Symptom Day 17 using trapezoidal approximation, which corresponds to a time frame of common cold onset to treatment day 15 (assuming treatment starts on Symptom Day 3

Model contains time-to-treatment stratum, previous influenza vaccination, alcohol consumption, working status and categorized baseline WURSS-11 score.

≤12 h v >12 to 24 h v >24 h

308

Pre-specified

Below the LS means difference were presented.

Primary

The mean daily total scores (imputed) were summed up from Symptom Day 1 to Symptom Day 17 using trapezoidal approximation, which corresponds to a time frame of common cold onset to treatment day 15 (assuming treatment starts on Symptom Day 3).

Mean daily total scores were derived per Symptom Day as described for the primary efficacy endpoint and were analysed per symptom day. Due to abundance of data for this secondary endpoint only the data of first symptom day is presented, data for all symptome days are presented in the enclosed graph in the attachment.

Secondary

Course of mean daily total scores from common cold onset to end-of-trial.

Mean daily group scores were derived analogously to mean daily total score by considering only WURSS-11 questions 2 to 8 for the symptom domain (i.e., aggregated for nasal, throat and item feeling tired) and WURSS-11 questions 9 and 10 for the QoL domain. Due to the abundance of data only the data of first symptom day is presented, all symptomeday data is presented in the enclosed graph in the attachment.

Secondary

Course of mean daily QoL scores from common cold onset to end-of-trial.

Remission was considered as present, if daily single item score of WURSS-11 question 1 was ≤1 together with only one symptom scored ≤3 and all other symptoms scored 0 of the considered day based on corresponding single item scores. Time to remission was then defined as the symptom day of first documented remission. A subject was censored at the time of last measurement if no remission was observed before.

Secondary

From common cold onset to end-of-trial.

The number of AEs and the number and percentage of subjects with at least one AE were tabulated by MedDRA system organ class (SOC) and preferred term (PT).

Secondary

Start of IMP intake at visit 2, ends at last study visit per subject. If the investigator becomes aware of an AE up to one week after the administration of the last IMP / rescue medication intake this has also to be documented.

AE recording started after first IMP administration and ended at last trial visit per subject, related AEs 1 week after last intake. Not recovered AEs were to be followed up until resolved or stabilized so that no further improvement could be expected.

At each visit, the investigator assessed by asking an open standard question (Have anything changed in your state of health since you last came to see me?) if any AEs (non-serious and serious) had occurred. Any AEs, spontaneously reported by the subject or by the subject’s relatives/delegates or observed by the investigator were to be recorded.

23.0

Safety Set